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Background: Zinc finger E-box binding homEeobox 1 (ZEB1) and ZEB2 are two anoikis-related transcription factors. The mRNA expressions of these two genes are significantly increased in kidney renal clear cell carcinoma (KIRC), which are associated with poor survival. Meanwhile, the mechanisms and clinical significance of ZEB1 and ZEB2 upregulation in KIRC remain unknown. Methods: Through the Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database, expression profiles, prognostic value and receiver operating characteristic curves (ROCs) of ZEB1 and ZEB2 were evaluated. The correlations of ZEB1 and ZEB2 with anoikis were further assessed in TCGA-KIRC database. Next, miRTarBase, miRDB, and TargetScan were used to predict microRNAs targeting ZEB1 and ZEB2, and TCGA-KIRC database was utilized to discern differences in microRNAs and establish the association between microRNAs and ZEBs. TCGA, TIMER, TISIDB, and TISCH were used to analyze tumor immune infiltration. Results: It was found that ZEB1 and ZEB2 expression were related with histologic grade in KIRC patient. Kaplan-Meier survival analyses showed that KIRC patients with low ZEB1 or ZEB2 levels had a significantly lower survival rate. Meanwhile, ZEB1 and ZEB2 are closely related to anoikis and are regulated by microRNAs. We constructed a risk model using univariate Cox and LASSO regression analyses to identify two microRNAs (hsa-miR-130b-3p and hsa-miR-138-5p). Furthermore, ZEB1 and ZEB2 regulate immune cell invasion in KIRC tumor microenvironments. Conclusions: Anoikis, cytotoxic immune cell infiltration, and patient survival outcomes were correlated with ZEB1 and ZEB2 mRNA upregulation in KIRC. ZEB1 and ZEB2 are regulated by microRNAs. [ABSTRACT FROM AUTHOR]

Introduction: Radiotherapy (RT) plays an indispensable role in postoperative breast cancer treatment. This study aimed to assess the feasibility of preoperative RT for stage III breast cancer by comparing preoperative RT with postoperative RT in terms of overall survival (OS). Methods: Based on the information in the Surveillance, Epidemiology, and End Results database from 2000 to 2018, patients with stage III breast cancer who had undergone radical surgery and RT were divided into two groups: a preoperative RT group and a postoperative RT group. OS was calculated using Kaplan-Meier analysis. The Cox proportional hazards model was used to evaluate independent factors associated with OS. Propensity score matching (PSM) was used to balance stratification factors. Results: In total, 9,605 patients were enrolled, of whom 9,456 received postoperative RT and 149 received preoperative RT. After a median follow-up of 72 months, postoperative RT was found to be superior to preoperative RT in terms of OS (p < 0.000). Compared to the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (OS: hazard ratio [HR] = 1.653, 95% confidence interval [CI]: 1.288–2.123, p < 0.000) and multivariate analyses (OS: HR = 1.409, 95% CI: 1.096–1.810, p = 0.007). After PSM, the OS of the postoperative RT group was superior to the OS in the preoperative RT group (p = 0.041). Compared with the postoperative RT group, the preoperative RT group showed a significantly higher risk of overall mortality without PSM in univariate (HR = 1.312, 95% CI: 1.010–1.704, p = 0.042) and multivariate analyses (HR = 1.466, 95% CI: 1.127–1.906, p = 0.004). Conclusion: Preoperative RT does not improve OS in patients with stage III breast cancer and has a worse prognosis. Preoperative RT has not changed the existing treatment paradigm in the current therapeutic context for patients with stage III breast cancer. [ABSTRACT FROM AUTHOR]

We performed a nested case-control study to investigate the incidence, treatment, and prognosis of central nervous system (CNS) relapse after allogenic hematopoietic stem cell transplantation (allo-HSCT) for acute myeloid leukemia (AML) and compared the outcomes of patients with CNS relapse following haploidentical donor (HID) HSCT versus identical sibling donor (ISD) HSCT. A total of 37 patients (HID-HSCT, 24; ISD-HSCT, 13) developed CNS relapse after transplantation between January 2009 and January 2019, with an incidence of 1.81%. The median time from transplantation to CNS relapse was 239 days. Pre-HSCT CNS involvement (HR 6.940, 95% CI 3.146–15.306, p <.001) was an independent risk factor for CNS relapse after allo-HSCT for AML. The 3-year overall survival (OS) for patients with CNS relapse was 60.3 ± 8.8%, which was significantly lower than that in the controls (81.5 ± 4.5%, p =.003). The incidence of CNS relapse was 1.64% for patients who received HID-HSCT and 2.55% for those who received ISD-HSCT (p =.193). There was no significant difference in OS between the HID-HSCT and ISD-HSCT subgroups among the patients with CNS relapse. In conclusion, CNS relapse is a rare but serious complication after allo-HSCT for AML, and the incidence and outcomes of patients with CNS relapse are comparable following HID-HSCT and ISD-HSCT. [ABSTRACT FROM AUTHOR]

To explore the incidence, risk factors, and outcomes of central nervous system (CNS) relapse after allogeneic hematopoietic stem cell transplantation (allo-HSCT) for acute lymphoblastic leukemia (ALL) and to compare the differences in CNS relapse between haploidentical donor HSCT (HID-HSCT) and HLA-identical sibling donor HSCT (ISD-HSCT). We performed a retrospective nested case-control study on patients with CNS relapse after allo-HSCT. The cumulative incidence of CNS relapse was 4.06% after allo-HSCT in ALL, with a significantly poor prognosis. The incidence was 3.91% and 5.36% in HID-HSCT and ISD-HSCT, respectively (p = .227). Among the patients with CNS relapse, the overall survival (OS) at 3 years was 56.2 ± 6.8% in the HID-HSCT subgroup and 76.9 ± 10.2% in the ISD-HSCT subgroup (p = .176). The 3-year cumulative incidence of systemic relapse was also comparable between the two subgroups (HID-HSCT, 40.6 ± 7.4%; ISD-HSCT, 13.3 ± 8.7%, respectively, p = .085). Younger age (p = .045), T-ALL (p = .035), hyperleukocytosis at diagnosis (p < .001), advanced disease stage at transplant (p < .001), pre-HSCT CNS involvement (p < .001), and absence of chronic graft vs host disease (cGVHD) (p < .001) were independent risk factors for CNS relapse after allo-HSCT. In conclusion, CNS relapse was a significant complication after allo-HSCT in ALL and was associated with poor prognosis. The incidences and outcomes were comparable between HID-HSCT and ISD-HSCT. [ABSTRACT FROM AUTHOR]

Background: Our study investigated the effect of lymph node (LN) noncompliance on the long-term prognosis of patients after laparoscopic total gastrectomy (LTG) and explored the risk factors of LN noncompliance. Methods: The clinicopathological data of gastric cancer (GC) patients who underwent LTG with D2 lymphadenectomy from June 2007 to December 2013 were prospectively collected and retrospectively analyzed. The effects of LN noncompliance on the long-term prognosis of patients with GC after LTG were explored. Results: The overall LN noncompliance rate was 51.9%. The survival rate of patients after LTG with LN compliance was significantly superior to that of patients with LN noncompliance (p = 0.013). The stratified analysis of TNM stage indicated that there was no difference between the OS of stage I patients with LN compliance and those with LN noncompliance; OS of stage II/III patients with LN compliance was significantly better than that of those with LN noncompliance. Cox regression analyses showed that LN noncompliance was an independent risk factor for OS. Logistic regression analysis showed that high BMI (≥ 25 kg/m2) was an independent risk factor for preoperative prediction of LN noncompliance in cStage II/III patients. Patients with a high BMI were more likely to have LN noncompliance during surgery, especially during the dissections of #6, #8a, and #12a LN stations. Conclusions: LN noncompliance was an independent risk factor for poor prognosis in patients with advanced gastric cancer (AGC) after LTG. Patients with high BMI were more likely to have LN noncompliance, especially during the dissections of #6, #8a, and #12a LN stations. LN tracing was recommended for these patients to reduce the rate of LN noncompliance. [ABSTRACT FROM AUTHOR]

Background: Increasing number of clinical studies have shown that laparoscopic distal gastrectomy (LDG) with D2 lymph node (LN) dissection is an effective method for the treatment of advanced gastric cancer (AGC). However, reports on the technical feasibility and oncology efficacy of laparoscopic total gastrectomy (LTG) in the treatment of AGC are rare. Methods: A retrospective analysis of the clinicopathologic data of 1313 patients with clinical stage of cT2-4aN0-3M0 undergoing laparoscopic radical gastrectomy with D2 LN dissection from June 2007 to December 2013 was performed. Noncompliance was defined as patients with more than one LN station absence as described in the protocol for D2 lymphadenectomy in the Japanese Gastric Cancer Association (JGCA). According to the literature, it was subdivided into LN compliance group (all LN stations were detected), minor LN noncompliance group (1–2 LN stations were not detected), major LN noncompliance group (more than 2 LN stations were not detected). Based on the LN noncompliance, the surgical indications of LTG were analyzed with LDG as control. Results: Among the 1313 patients, 197 (39.20%) patients and 321(39.71%) patients in the LDG group and the LTG group had minor LN noncompliance, 59(11.70%) patients and 163(20.10%) patients had major LN noncompliance. The difference in the extent of LN noncompliance between the two groups was statistically significant (p < 0.001). COX proportional hazards regression analysis elucidated that the LN noncompliance was an independent prognostic factor for overall survival (OS). BMI ≥ 25 kg/m2 and the history of previous abdominal surgery (PAS) were independent risk factors for major LN noncompliance in LTG group (p < 0.05), with which patients were defined as a LN noncompliance high-risk group. With the exception of LN noncompliance high-risk group, the difference in the extent of LN noncompliance between LTG group and LDG group was still statistically significant (p = 0.008). Tumor diameter > 60 mm is a preoperative risk factor for station #5 LN noncompliance, and no preoperative risk factors for station #6 LN noncompliance were found, with which patients were defined as LN noncompliance middle-risk group. Conclusion: LN noncompliance is an independent prognostic factor for poor prognosis in patients after LTG. Based on this finding, patients with BMI ≥ 25 kg/m2, history of PAS and tumor diameter > 60 mm in the advanced stage of upper-middle gastric cancer represent high/middle-risk groups with LN noncompliance in LTG surgery, which should be carefully selected. [ABSTRACT FROM AUTHOR]

Background: Population-based estimates of the incidence and prognosis of brain metastases at diagnosis of hepatocellular carcinoma (HCC) are lacking. The aim of this study was to characterize the incidence proportion and survival of newly diagnosed hepatocellular carcinoma with brain metastases (HCCBM). Materials and methods: Data from Surveillance, Epidemiology, and End Results (SEER) program between 2010 and 2014 was evaluated. Patients with HCCBM were included. Multivariable logistic and Cox regression were performed to identify predictors of the presence of brain metastases at diagnosis and prognostic factors of overall survival (OS). We also built a nomogram based on Cox model to predict prognosis for HCCBM patients. Results: We identified 97 patients with brain metastases at the time of diagnosis of HCC, representing 0.33% of the entire cohort. Logistic regression showed patients with bone or lung metastases had greater odds of having brain metastases at diagnosis. Median OS for HCCBM was 2.40 months. Cox regression revealed unmarried and bone metastases patients suffered significantly shorter survival time. A nomogram was developed with internal validation concordance index of 0.639. Conclusions: This study provided population-based estimates of the incidence and prognosis for HCCBM patients. The nomogram could be a convenient individualized predictive tool for prognosis. [ABSTRACT FROM AUTHOR]

Aims: Previous studies have found that long noncoding RNA taurine upregulated gene 1 (TUG1) can regulate osteosarcoma cells apoptosis and proliferation; the aim of this study was to investigate the clinical significance of TUG1 in osteosarcoma.Subjects and Methods: The expression of TUG1 was detected by real-time and quantitative polymerase chain reaction assay in 94 pairs of tumor tissues and corresponding noncancerous bone tissues of osteosarcoma patients. Its correlations with clinicopathologic features were analyzed, and the significance of TUG1 as a prognostic factor was determined.Results: This study shows that the expression of TUG1 in osteosarcoma tissues was significantly higher than that in adjacent normal bone tissues. Upregulation of TUG1 was significantly correlated with the larger tumor size and advanced tumor-node-metastases stage of osteosarcoma patients. Kaplan-Meier curve showed a decreased overall survival time of osteosarcoma patients with high TUG1 expression. Moreover, univariate and multivariate analyses suggested that low-expression level of TUG1 was an independent poor prognostic indicator for osteosarcoma patients.Conclusions: In conclusion, our data support TUG1 as a potential prognostic predictor and gene therapy target with its high expression in tumor tissues and its association with carcinogenesis and progression in osteosarcoma. [ABSTRACT FROM AUTHOR]

Aim: To investigate oncologic efficacy of prophylactic laparoscopic superior mesenteric vein (No. 14v) lymph node (LN) dissection for lower-third gastric cancer (LTGC).Methods: We retrospectively collected data from 757 patients who underwent laparoscopic-assisted distal gastrectomy for LTGC. Of these patients, 102 underwent 14v LN dissection (14vD+ group), and the remaining 655 patients did not undergo 14v LN dissection (14vD- group). The outcomes were compared using a 1:1 propensity score matching method.Results: After matching, 93 patients from the 14vD+ group and 93 patients from the 14vD- group with similar clinicopathological characteristics were compared. Before matching, the overall survival (OS) was similar between the two groups (P = 0.742). After matching, the OS was greater in the 14vD+ group (P = 0.025). The status of 14v dissection was not a significant prognostic factor in the survival analyses, both before and after matching. However, a stratified analysis according to the independent factors in the OS showed that the OS in the 14vD+ group was higher than that in the 14vD- group for cT2-3 patients after matching. The forest plot of OS showed that after matching the 14vD+ group had a significantly higher 3-year OS rate than the 14vD- group in cT2-3 patients. The distribution of the therapeutic index demonstrated that the index of 14v LN was similar to those of Nos. 1, 7, 8a, 9, and 11p after matching.Conclusions: Adding laparoscopic 14v dissection for laparoscopic-assisted radical distal gastrectomy was safe and might improve the OS for clinically advanced LTGC without serosal invasion. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) are pivotal components of tumor microenvironment (TME), and senescent TAMs contribute to the alternation of the profiles of TME. However, the potential biological mechanisms and the prognosis value of senescent macrophages are largely unknown, especially in bladder cancer (BLCA). Based on the single-cell RNA sequencing of a primary BLCA sample, 23 macrophage-related genes were identified. Genomic difference analysis, LASSO, and Cox regression were used to develop the risk model. TCGA-BLCA cohort (n = 406) was utilized as the training cohort, and then, three independent cohorts (n = 90, n = 221, n = 165) from Gene Expression Omnibus, clinical samples from the local hospital (n = 27), and in vitro cell experiments were used for external validation. Aldo-keto reductase family 1 member B (AKR1B1), inhibitor of DNA binding 1 (ID1), and transforming growth factor beta 1 (TGFB1I1) were determined and included in the predictive model. The model serves as a promising tool to evaluate the prognosis in BLCA (pooled hazard ratio = 2.51, 95% confidence interval = [1.43; 4.39]). The model was also effective for the prediction of immunotherapeutic sensitivity and chemotherapy treatment outcomes, which were further confirmed by IMvigor210 cohort (P < 0.01) and GDSC dataset, respectively. Twenty-seven BLCA samples from the local hospital proved that the risk model was associated with the malignant degree (P < 0.05). At last, the human macrophage THP-1 and U937 cells were treated with H2O2 to mimic the senescent process in macrophage, and the expressions of these molecules in the model were detected (all P < 0.05). Overall, a macrophage cell senescence-related gene signature was constructed to predict the prognosis, immunotherapeutic response, and chemotherapy sensitivity in BLCA, which provides novel insights to uncover the underlying mechanisms of macrophage senescence. [ABSTRACT FROM AUTHOR]

Background Signal peptide-Cub-Epidermal growth factor domain-containing protein 1 (SCUBE1), a marker for coagulation, is secreted under hypoxia and inflammatory conditions from platelet α granules. This study was designed to determine the associations of serum SCUBE1 concentrations with trauma severity and prognosis after severe traumatic brain injury. Methods Serum SCUBE1 concentrations of 113 patients and 113 controls were measured. An unfavorable outcome was defined as Glasgow Outcome Scale score of 1–3. Results Serum SCUBE1 concentrations were significantly higher in patients than in controls (15.5 ± 6.0 vs. 1.1 ± 0.3 ng/ml, P < 0.001) and were associated with Glasgow coma scale scores (r = − 0.439, P < 0.001) and blood platelet count (r = 0.420, P < 0.001). SCUBE1 was identified as an independent prognostic marker of 6-month unfavorable outcome (odds ratio, 1.357; 95% confidence interval, 1.159–1.589; P < 0.001), and had high predictive value according to receiver operating characteristic curve (area under curve, 0.830; 95% confidence interval, 0.748–0.890; P < 0.001). Conclusions Increased serum SCUBE1 concentrations are associated highly with trauma severity, platelet activation and poor outcome, suggesting that SCUBE1 might be a novel prognostic biomarker after traumatic brain injury. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of intraoperative lymph node (LN) dissection and postoperative adjuvant chemotherapy on the overall survival (OS) of gastric cancer (GC) patients and their reciprocity. Methods: LN noncompliance was defined as the absence of more than one LN station, as described in the protocol for D2 lymphadenectomy in the Japanese Gastric Cancer Association. The definition of adjuvant chemotherapy (AC) noncompliance was that the chemotherapy planned dose does not meet the requirements. Results: Kaplan–Meier survival curves showed that the OS of patients with major LN noncompliance was significantly lower than that of patients with nonmajor LN noncompliance, and the OS of AC noncompliance patients was significantly lower than that of AC compliance patients. If there was nonmajor LN noncompliance during surgery, the OS of patients with AC compliance was significantly higher than that of patients with AC noncompliance (P = 0.035). In the case of major LN noncompliance during surgery, there was no statistically significant difference in OS between those with AC compliance and those with AC noncompliance (P = 0.682). Multivariate Cox regression analysis including AC noncompliance indicated that major LN noncompliance was an independent prognostic factor for poor OS (P = 0.012), while AC noncompliance was not an independent prognostic factor for OS (P = 0.609). Conclusion: Adequate lymph node dissection and adjuvant chemotherapy are both key steps to improve the awful prognosis of GC patients. Adjuvant chemotherapy may fail to remedy the poor prognosis caused by major LN noncompliance. [ABSTRACT FROM AUTHOR]

Background: Surgical quality control is a crucial determinant of evaluating the tumor efficacy. Objective: To assess the ClassIntra grade for quality control and oncological outcomes of robotic radical surgery for gastric cancer (GC). Methods: Data of patients undergoing robotic radical surgery for GC at a high-volume center were retrospectively analyzed. Patients were categorized into two groups, the intraoperative adverse event (iAE) group and the non-iAE group, based on the occurrence of intraoperative adverse events. The iAEs were further classified into five sublevels (ranging from I to V according to severity) based on the ClassIntra grade. Surgical performance was assessed using the Objective Structured Assessment of Technical Skill (OSATS) and the General Error Reporting Tool. Results: This study included 366 patients (iAE group: n = 72 [19.7%] and non-iAE group: n = 294 [80.3%]). The proportion of ClassIntra grade II patients was the highest in the iAE group (54.2%). In total and distal gastrectomies, iAEs occurred most frequently in the suprapancreatic area (50.0% and 54.8%, respectively). In total gastrectomy, grade IV iAEs were most common during lymph node dissection in the splenic hilum area (once for bleeding [grade IV] and once for injury [grade IV]). The overall survival (OS) and disease-free survival of the non-iAE group were significantly better than those of the iAE group (Log rank P < 0.001). Uni- and multi-variate analyses showed that iAEs were key prognostic indicators, independent of tumor stage and adjuvant chemotherapy (P < 0.001). Conclusion: iAEs in patients who underwent robotic radical gastrectomy significantly correlated with the occurrence of postoperative complications and a poor long-term prognosis. Therefore, utilization and inclusion of ClassIntra grading as a crucial surgical quality control and prognostic indicator in the routine surgical quality evaluation system are recommended. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of preoperative sarcopenia on the short-term and long-term outcomes in older patients with locally advanced gastric cancer (LAGC). Methods: Clinicopathological data of older patients with LAGC who underwent radical surgery were retrospectively analyzed. Sarcopenia was defined as a skeletal muscle index of less than 36.4 cm2/m2 for men and less than 28.4 cm2/m2 for women. Comparing the postoperative complications and survival between sarcopenia and non-sarcopenia groups using multicenter data. Results: A total of 406 older patients with LAGC were included in the analysis, including 145 (35.7%) with sarcopenia and 261 (64.3%) with non-sarcopenia. Multivariate logistic regression analysis showed that sarcopenia was an independent risk factor for postoperative complications with CD grade ≥ II (OR 1.616; P < 0.05). Kaplan–Meier survival curve analysis showed that the 5-year overall survival (OS) and 5-year recurrence-free survival (RFS) in the sarcopenia group were lower than those in the non-sarcopenia group (P both < 0.05). Multivariate Cox regression analyses showed that sarcopenia was an independent prognostic factor for 5-year OS and RFS (P both < 0.05). The 5-year recurrence rate in the sarcopenia group was 57.2%, which was significantly higher than that in the non-sarcopenia group (46.4%; P = 0.036). Recurrence pattern analysis showed that the incidence of distant metastases in patients with sarcopenia (42.8%) was significantly higher than non-sarcopenia (31.4%; P = 0.022). Conclusion: Sarcopenia serves as a valuable predictor of both short-term and long-term outcomes in older patients with LAGC. Therefore, the significance of assessing preoperative nutritional status and implementing thorough postoperative follow-up for older LAGC patients with sarcopenia should be emphasized. [ABSTRACT FROM AUTHOR]

Background: Our study investigated the effect of lymph node (LN) noncompliance on the long-term prognosis of patients after laparoscopic total gastrectomy (LTG) and explored the risk factors of LN noncompliance.Methods: The clinicopathological data of gastric cancer (GC) patients who underwent LTG with D2 lymphadenectomy from June 2007 to December 2013 were prospectively collected and retrospectively analyzed. The effects of LN noncompliance on the long-term prognosis of patients with GC after LTG were explored.Results: The overall LN noncompliance rate was 51.9%. The survival rate of patients after LTG with LN compliance was significantly superior to that of patients with LN noncompliance (p = 0.013). The stratified analysis of TNM stage indicated that there was no difference between the OS of stage I patients with LN compliance and those with LN noncompliance; OS of stage II/III patients with LN compliance was significantly better than that of those with LN noncompliance. Cox regression analyses showed that LN noncompliance was an independent risk factor for OS. Logistic regression analysis showed that high BMI (≥ 25 kg/m2) was an independent risk factor for preoperative prediction of LN noncompliance in cStage II/III patients. Patients with a high BMI were more likely to have LN noncompliance during surgery, especially during the dissections of #6, #8a, and #12a LN stations.Conclusions: LN noncompliance was an independent risk factor for poor prognosis in patients with advanced gastric cancer (AGC) after LTG. Patients with high BMI were more likely to have LN noncompliance, especially during the dissections of #6, #8a, and #12a LN stations. LN tracing was recommended for these patients to reduce the rate of LN noncompliance. [ABSTRACT FROM AUTHOR]

Background: Well-designed retrospective studies (RSs) and small-sample prospective studies (PSs) evaluating the efficacy of interventions have received much attention. This study was designed to evaluate the differences between well-designed RSs and small-sample randomized controlled trials based on the efficacy of laparoscopic distal gastrectomy (LDG) and open distal gastrectomy (ODG) for advanced gastric cancer (GC).Methods: The clinicopathological data of 1360 patients with GC who underwent DG were analysed. After propensity score matching (1:1), 380 cases (ODG = 190, LDG = 190) were finally selected in a RS. Meanwhile, data from 120 patients (ODG = 60, LDG = 60) who enrolled in a PS were analysed.Results: In the PS, the LDG group had less intraoperative blood loss, shorter time to first flatus, and shorter time to fluid diet than the ODG group. In the RS, the LDG group had less intraoperative blood loss, and a shorter postoperative hospital stay than the ODG group. In the PS, the 3-year overall survival (OS) rate was 83.3% in the LDG group and 83.2% in the ODG group (p = 0.877). In the RS, the 3-year OS rate was 68.7% in the LDG group and 66.6% in the ODG group (p = 0.752). No significant interactions were observed between the two groups and any of the variables examined, either in the PS or RS. The recurrence patterns were similar in the two groups. Furthermore, Cox regression analysis showed that surgical method (LDG/ODG) was not a prognostic factor affecting OS or DFS, either prospectively or retrospectively.Conclusions: The oncologic efficacy of laparoscopic and open distal gastrectomy for advanced GC is comparable. Well-designed RSs can be similar to small sample of PSs in assessing long-term oncologic outcomes of surgical interventions, but the short-term outcomes obtained should be treated with caution. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is one of the most lethal malignancies with an extremely poor prognosis. In this study, we aim to construct a long noncoding RNA (lncRNA)-based panel biomarker to predict the overall survival of PC patients. The lncRNA expression profiles of PC samples were extracted from The Cancer Genome Atlas (TCGA-PAAD, n = 176) and International Cancer Genome Consortium (PACA-CA, n = 180). We then developed a risk score model according to the lncRNAs expressions from the TCGA-PAAD cohort and further validated it in the PACA-CA cohort. The potential biological functions for the prognostic lncRNAs were investigated using gene set enrichment analysis (GSEA). In the TCGA-PAAD cohort, three lncRNAs (AC009014.3, RP11-48O20.4, and UCA1) were found to be strongly associated with the prognosis of PC. These lncRNAs were integrated to build a three-lncRNA prognostic model that could divide individuals into low- and high-risk groups. Patients of TCGA-PAAD cohort in the high-risk group showed a poorer overall survival than those in the low-risk group (median: 17.3 months vs. 30.4 months, log-rank p < 0.001). Similar results were documented in the PACA-CA cohort (median: 15.2 months vs. 21.0 months, log-rank p < 0.001) and in the stratified analyses by patients' age and TNM stage. In addition, the signature exhibited an independent prognostic power and was significantly correlated with tumor relapse and patients' response to chemotherapy. GSEA indicated that the three-lncRNA signature may be involved in many known biological functions in cancer, especially the epithelial mesenchymal transformation. In conclusion, the identified three-lncRNA signature in our study may serve as a robust and useful prognostic biomarker in PC patients. [ABSTRACT FROM AUTHOR]

Objectives: To investigate the prognostic values of preoperative platelet‐to‐lymphocyte ratio (PLR) and platelet‐related indices in advanced hypopharyngeal squamous cell carcinoma (HPSCC). Methods: The data of 247 eligible advanced HPSCC patients were reviewed retrospectively. Pretreatment haematological parameters were categorised into two groups based on the result of X‐tile, and several variates were assessed using chi‐square test, Kaplan‐Meier method, Cox univariate and multivariate analysis. Results: The optimal cut‐off points of 171.4 for PLR, 260 × 109/L for platelet, 10.4 fL for mean platelet volume (MPV) and 16.5% for platelet distribution width were defined. The haematological parameters PLR and MPV, postoperative metastasis and internal jugular vein invasion were statistically significant in OS and DFS analyses (P <.05). The high PLR (>171.4) or high MPV (>10.4 fL) was significantly associated with worse OS and DFS (P <.05). Conclusions: The preoperative levels of PLR and MPV could be considered as independent prognostic predictors in patients with advanced HPSCC. [ABSTRACT FROM AUTHOR]

Background: Few studies have investigated the efficacy of comprehensive therapies, including immunotherapy, for gastric cancer with synchronous liver metastases (GCLM). We retrospectively compared the effect of immunochemotherapy and chemotherapy alone as conversion therapies on the oncological outcomes of patients with GCLM. Methods: The clinicopathological data of 100 patients with GCLM from February 2017 to October 2021 at our institution were retrospectively analyzed. Patients were divided into immunochemotherapy (n = 33) and chemotherapy‐alone (n = 67) groups. Results: Baseline clinicopathological data did not differ significantly between the two groups. The immunochemotherapy group had a higher overall response rate (59.4% vs. 44.0%, p = 0.029) and disease control rate (71.9% vs. 49.2%, p = 0.036) than the chemotherapy group. The immunochemotherapy group showed better tumor regression in the gastric mass, metastatic lymph nodes, and liver lesions than the chemotherapy group. Ten (30.3%) patients in the immunochemotherapy group and 13 (19.4%) patients in the chemotherapy group underwent surgery after conversion therapy. However, the difference was not statistically significant. The overall survival (OS) and progression‐free survival (PFS) rates were better in the immunochemotherapy group than in the chemotherapy group. Treatment‐related adverse events occurred in 24 (72.7%) and 47 (70.1%) patients in the immunochemotherapy and chemotherapy groups, respectively. Conclusions: As a conversion therapy for GCLM, immunotherapy yielded better primary and metastatic tumor regression and survival benefits, with no increase in adverse events compared to chemotherapy. [ABSTRACT FROM AUTHOR]

The effectiveness of neoadjuvant immune checkpoint inhibitor (ICI) therapy is confirmed in clinical trials; however, the patients suitable for receiving this therapy remain unspecified. Previous studies have demonstrated that the tumor microenvironment (TME) dominates immunotherapy; therefore, an effective TME classification strategy is required. In this study, five crucial immunophenotype‐related molecules (WARS, UBE2L6, GZMB, BATF2, and LAG‐3) in the TME are determined in five public gastric cancer (GC) datasets (n = 1426) and an in‐house sequencing dataset (n = 79). Based on this, a GC immunophenotypic score (IPS) is constructed using the least absolute shrinkage and selection operator (LASSO) Cox, and randomSurvivalForest. IPSLow is characterized as immune‐activated, and IPSHigh is immune‐silenced. Data from seven centers (n = 1144) indicate that the IPS is a robust and independent biomarker for GC and superior to the AJCC stage. Furthermore, patients with an IPSLow and a combined positive score of ≥5 are likely to benefit from neoadjuvant anti‐PD‐1 therapy. In summary, the IPS can be a useful quantitative tool for immunophenotyping to improve clinical outcomes and provide a practical reference for implementing neoadjuvant ICI therapy for patients with GC. [ABSTRACT FROM AUTHOR]

The prognosis of acute myeloid leukemia (AML) with normal karyotype is further determined by specific genetic alterations. The optimal post-remission therapy (PRT) in younger patients within this group after first complete remission (CR1) remains to be determined. We report a retrospective evaluation of PRT approaches in 223 patients under the age of 60 years old with intermediate-risk AML in CR1. Patients receiving allogenic hematopoietic stem cell transplantation (alloHSCT) obtained improved overall survival (OS) than patients who treated with chemotherapy (5-year 61.6 ± 5.2% versus 41.1 ± 5.3%, p = 0.004). AlloHSCT led to fewer cases of relapse (hazard ratio [HR] 0.14, p < 0.001) and increased the relapse-free survival (RFS, HR 0.45, p < 0.001). With alloHSCT, the outcome of patients who reached negative minimal residual disease after 2 cycles of consolidation could be further improved with an increased OS of 66% and RFS of 61%. Nucleophosmin-1 (NPM1) mutation negative, CCAAT/enhancer binding protein alpha (CEBPA) double mutation negative, and FLT-3 internal tandem duplication negative (NPM1mut-negCEBPAdm-negFLT3-ITDneg) patients had a significantly longer RFS with alloHSCT. In conclusion, our results provide additional evidence that alloHSCT is preferential PRT in patients with intermediate-risk AML that are under the age of 60 years old in CR1. [ABSTRACT FROM AUTHOR]

Objective To investigate the safety and efficacy of transcatheter arterial chemoembolization ( TACE) with embospheres for the treatment of unresectable hepatocellular carcinoma ( HCC). Methods Patients with unresectable HCC who were treated with TACE followed by embosphere treatment (Embo- TACE) or conventional TACE (c TACE) between May 2010 and March 2014 were retrospectively included in this study. The Embo- TACE group received lipiodol and chemotherapeutic agent emulsion, followed by embospheres. The c TACE group received lipiodol and chemotherapeutic agent emulsion, followed by gelatin sponge pellets. Time to progression ( TTP), overall survival ( OS), overall response rate ( ORR), and safety were compared between the two groups. Univariate and multivariate regression analyses of the factors affecting survival were conducted. Results The median TTP and OS in the Embo- TACE group were significantly longer than those in the c TACE group ( TPP: 7.0 months vs 5.4 months, P = 0.035; OS: 15 months vs 12 months, P = 0.032). Seven days after the first TACE treatment, alanine aminotransferase level was higher in the c TACE group than in the Embo- TACE group ( P = 0.015). The ORR did not significantly differ between the two groups ( P = 0.827). Additional therapy and local responses one month after the first TACE treatment were associated with OS. Conclusions Embo- TACE resulted in a significant improvement in TTP and OS for patients with unresectable HCC, compared with c TACE. Furthermore, Embo- TACE was better tolerated. Additional therapy and local responses one month after the first TACE were independent prognostic factors for OS. [ABSTRACT FROM AUTHOR]

Background: Tumor necrosis factor alpha-induced protein 2 (TNFAIP2), a TNFα-inducible gene, appears to participate in inflammation, immune response, hematopoiesis, and carcinogenesis. However, the potential role of TNFAIP2 in the development of acute myeloid leukemia (AML) remains unknow yet. Therefore, we aimed to study the biological role of TNFAIP2 in leukemogenesis.Methods: TNFAIP2 mRNA level, prognostic value, co-expressed genes, differentially expressed genes, DNA methylation, and functional enrichment analysis in AML patients were explored via multiple public databases, including UALCAN, GTEx portal, Timer 2.0, LinkedOmics, SMART, MethSurv, Metascape, GSEA and String databases. Data from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus (GEO) and Beat AML database were used to determine the associations between TNFAIP2 expression and various clinical or genetic parameters of AML patients. Moreover, the biological functions of TNFAIP2 in AML were investigated through in vitro experiments.Results: By large-scale data mining, our study indicated that TNFAIP2 was differentially expressed across different normal and tumor tissues. TNFAIP2 expression was significantly increased in AML, particularly in French-American-British (FAB) classification M4/M5 patients, compared with corresponding control tissues. Overexpression of TNFAIP2 was an independent poor prognostic factor of overall survival (OS) and was associated with unfavorable cytogenetic risk and gene mutations in AML patients. DNA hypermethylation of TNFAIP2 at gene body linked to upregulation of TNFAIP2 and inferior OS in AML. Functional enrichment analysis indicated immunomodulation function and inflammation response of TNFAIP2 in leukemogenesis. Finally, the suppression of TNFAIP resulted in inhibition of proliferation by altering cell-cycle progression and increase of cell death by promoting early and late apoptosis in THP-1 and U937AML cells.Conclusion: Collectively, the oncogenic TNFAIP2 can function as a novel biomarker and prognostic factor in AML patients. The immunoregulation function of TNFAIP2 warrants further validation in AML. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.Methods: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.Results: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.Conclusion: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy.Graphical abstract: Adjuvant chemotherapy following curative surgery for locally advanced gastric cancer (AGC) significantly improves long-term patient prognosis. However, delayed chemotherapy (DC), in which patients are unable to receive timely treatment, is a common phenomenon in clinical practice for various reasons. This study aimed to investigate the impact of DC on the prognosis of patients with stage II–III locally AGC and explore the associated risk factors.Data from four prospective studies were included in the pooled analysis. The planned chemotherapy (PC) group was defined as the time interval between surgery and the first chemotherapy ≤ 49 d, while the DC group was defined as the time interval between surgery and chemotherapy > 49 d. The prognosis, recurrence, and risk factors were compared, and a nomogram for predicting DC was established.In total, 596 patients were included, of whom 531 (89.1%) had PC and 65 (10.9%) had DC. Survival analysis revealed that the 5-year overall survival (OS) and disease-free survival (DFS) were significantly lower in the DC group than those in the PC group (log-rank P < 0.001). Cox univariable and multivariable analyses showed that DC was an independent risk factor for OS and DFS in stage II–III patients (P < 0.05). Based on the significant factors for DC, a prediction model was established that had a good fit, high accuracy (AUC = 0.780), and clinical applicability in both the training and validation sets.Delayed chemotherapy after gastrectomy is associated with poor long-term prognosis in patients with locally advanced stage II–III GC disease. But standardized, full-cycle adjuvant chemotherapy after surgery may play a remedial role, and can to a certain extent compensate the poor effects caused by delayed chemotherapy. [ABSTRACT FROM AUTHOR]

Immunosenescence refers to the immune system undergoing a series of degenerative changes with advancing age and is tightly associated with the initiation and progression of cancers. However, the immunosenescence-related genes as critical biomarkers for bladder cancer (BLCA) have not been systematically analyzed. We retrieved the immunosenescence-related genes from the public database and verified their association with hallmarks of immunosenescence based on The Cancer Genome Atlas (TCGA) cohort. Through gene pairing, Lasso, and univariate Cox regression, an 8-gene pair model was constructed to evaluate the overall survival of BLCA, which was then validated in the training cohort (P < 0.001 , n = 396), two external validation cohorts (P < 0.05 , n = 165 ; P < 0.001 , n = 224), and local samples (P < 0.05 , n = 10). We also downloaded the clinical information and gene expression matrices of other 32 different cancers from TCGA. The established model showed significant predictive value for the prognosis in 15 cancers (P < 0.05). The risk model could also serve as a promising predictor for immunotherapeutic response, which has been verified by the TIDE algorithm (P < 0.05), IMvigor210 dataset (P < 0.01 , n = 298), and other two datasets correlated with immunotherapy (P < 0.05 , n = 56 ; P = 0.17 , n = 27). The TCGA dataset, in vitro cell experiments, and pan-cancer analysis displayed that the gene signature was associated with cisplatin sensitivity (P < 0.05). Overall, we proposed a novel immunosenescence-related gene signature to predict prognosis, immunotherapeutic response, and cisplatin sensitivity of BLCA, which were validated in different independent cohorts, local samples, and pan-cancer analyses. [ABSTRACT FROM AUTHOR]

Background: In bladder cancer, up to 70% of patients will relapse after resection within 5 years, in which the mechanism underlying the recurrence remains largely unclear. Methods: Quantitative real-time PCR, western blot and immunohistochemistry were conducted. The assays of tumor sphere formation and tumor xenograft were further performed to assess the potential biological roles of ATF5 (activating transcription factor 5). Chromatin immunoprecipitation-qPCR and luciferase activity assays were carried out to explore the potential molecular mechanism. A two-tailed paired Student's t-test, χ2 test, Kaplan Meier and Cox regression analyses, and Spearman's rank correlation coefficients were used for statistical analyses. Results: ATF5 is elevated in bladder urothelial cancer (BLCA) tissues, especially in recurrent BLCA, which confers a poor prognosis. Overexpressing ATF5 significantly enhanced, whereas silencing ATF5 inhibited, the capability of tumor sphere formation in bladder cancer cells. Mechanically, ATF5 could directly bind to and stimulate the promoter of DVL1 gene, resulting in activation of Wnt/β-catenin pathway. Conclusions: This study provides a novel insight into a portion of the mechanism underlying high recurrence potential of BLCA, presenting ATF5 as a prognostic factor or potential therapeutic target for preventing recurrence in BLCA. [ABSTRACT FROM AUTHOR]

Background: Isobutyryl-CoA dehydrogenase deficiency (IBDD) is a rare autosomal recessive metabolic disorder resulting from variants in ACAD8, and is poorly understood, as only dozens of cases have been reported previously. Based on a newborn screening program, we evaluated the incidence, phenotype and genotype of IBDD as well as the prognosis. Moreover, we reviewed the variant spectrum in ACAD8 associated with IBDD. Methods: Forty unrelated patients with IBDD were retrospectively screened for newborns between Jan 2012 and Dec 2020. Tandem mass spectrometry (MS/MS) was used to determine the concentrations of C4-acylcarnitine, C4/C2 (acetylcarnitine), and C4/C3 (propionylcarnitine). All suspected cases were genetically tested by metabolic genes panel. Results: The incidence of IBDD here was 1: 62,599. All patients presented continuously elevated C4-acylcarnitine levels with higher ratios of C4/C2 and C4/C3. Isobutyrylglycine occurred in only 8 patients. During follow-up, four patients had a transient motor delay, and two patients had growth delay. Notably, one case harbored both ACAD8 compound heterozygous variants and a KMT2A de novo variant (c.2739del, p.E914Rfs*35), with IBDD and Wiedemann–Steiner syndrome together, had exact severe global developmental delay. All patients were regularly monitored once they were diagnosed, and each patient gradually had a normal diet after 6 months of age. After 3–108 months of follow-up, most individuals were healthy except the case harboring the KMT2A variant. A total of 16 novel variants in ACAD8, c.4_5delCT, c.109C > T, c.110–2A > T, c.236G > A, c.259G > A, c.381–14G > A, c.413delA, c.473A > G, c.500delG, c.758 T > G, c.842–1G > A, c.911A > T, c.989G > A, c.1150G > C, c.1157A > G and c.1165C > T, were identified. Along with a literature review on 51 ACAD8 variants in 81 IBDD patients, we found that the most common variant was c.286G > A (27.2%), which has been observed solely in the Chinese population to date, followed by c.1000C > T (8.6%), c.1176G > T (3.7%) and c.455 T > C (3.1%). Conclusion: The concentration of C4-acylcarnitine in NBS plus subsequent genetic testing is necessary for IBDD diagnosis. Both the genotypes and ACAD8 variants in IBDD are highly heterogeneous, and no significant correlations between genotype and phenotype are present here in patients with IBDD. Our IBDD cohort with detaied clinical characteristics, genotypes and long-term prognosis will be helpful for the diagnosis and management of patients with IBDD in the future. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer was one of the leading causes of female deaths. Patients with OC were essentially incurable and portends a poor prognosis, presumably because of profound genetic heterogeneity limiting reproducible prognostic classifications.Methods: We comprehensively analyzed an ovarian cancer single-cell RNA sequencing dataset, GSE118828, and identified nine major cell types. Relationship between the clusters was explored with CellPhoneDB. A malignant epithelial cluster was confirmed using pseudotime analysis, CNV and GSVA. Furthermore, we constructed the prediction model (i.e., RiskScore) consisted of 10 prognosis-specific genes from 2397 malignant epithelial genes using the LASSO Cox regression algorithm based on public datasets. Then, the prognostic value of Riskscore was assessed with Kaplan-Meier survival analysis and time-dependent ROC curves. At last, a series of in-vitro assays were conducted to explore the roles of IL4I1, an important gene in Riskscore, in OC progression.Results: We found that macrophages possessed the most interaction pairs with other clusters, and M2-like TAMs were the dominant type of macrophages. C0 was identified as the malignant epithelial cluster. Patients with a lower RiskScore had a greater OS (log-rank P < 0.01). In training set, the AUC of RiskScore was 0.666, 0.743 and 0.809 in 1-year, 3-year and 5-year survival, respectively. This was also validated in another two cohorts. Moreover, downregulation of IL4I1 inhibited OC cells proliferation, migration and invasion.Conclusions: Our work provide novel insights into our understanding of the heterogeneity among OCs, and would help elucidate the biology of OC and provide clinical guidance in prognosis for OC patients. [ABSTRACT FROM AUTHOR]

Background: Isobutyryl-CoA dehydrogenase deficiency (IBDD) is a rare autosomal recessive metabolic disorder resulting from variants in ACAD8, and is poorly understood, as only dozens of cases have been reported previously. Based on a newborn screening program, we evaluated the incidence, phenotype and genotype of IBDD as well as the prognosis. Moreover, we reviewed the variant spectrum in ACAD8 associated with IBDD. Methods: Forty unrelated patients with IBDD were retrospectively screened for newborns between Jan 2012 and Dec 2020. Tandem mass spectrometry (MS/MS) was used to determine the concentrations of C4-acylcarnitine, C4/C2 (acetylcarnitine), and C4/C3 (propionylcarnitine). All suspected cases were genetically tested by metabolic genes panel. Results: The incidence of IBDD here was 1: 62,599. All patients presented continuously elevated C4-acylcarnitine levels with higher ratios of C4/C2 and C4/C3. Isobutyrylglycine occurred in only 8 patients. During follow-up, four patients had a transient motor delay, and two patients had growth delay. Notably, one case harbored both ACAD8 compound heterozygous variants and a KMT2A de novo variant (c.2739del, p.E914Rfs*35), with IBDD and Wiedemann–Steiner syndrome together, had exact severe global developmental delay. All patients were regularly monitored once they were diagnosed, and each patient gradually had a normal diet after 6 months of age. After 3–108 months of follow-up, most individuals were healthy except the case harboring the KMT2A variant. A total of 16 novel variants in ACAD8, c.4_5delCT, c.109C > T, c.110–2A > T, c.236G > A, c.259G > A, c.381–14G > A, c.413delA, c.473A > G, c.500delG, c.758 T > G, c.842–1G > A, c.911A > T, c.989G > A, c.1150G > C, c.1157A > G and c.1165C > T, were identified. Along with a literature review on 51 ACAD8 variants in 81 IBDD patients, we found that the most common variant was c.286G > A (27.2%), which has been observed solely in the Chinese population to date, followed by c.1000C > T (8.6%), c.1176G > T (3.7%) and c.455 T > C (3.1%). Conclusion: The concentration of C4-acylcarnitine in NBS plus subsequent genetic testing is necessary for IBDD diagnosis. Both the genotypes and ACAD8 variants in IBDD are highly heterogeneous, and no significant correlations between genotype and phenotype are present here in patients with IBDD. Our IBDD cohort with detaied clinical characteristics, genotypes and long-term prognosis will be helpful for the diagnosis and management of patients with IBDD in the future. [ABSTRACT FROM AUTHOR]

The tight relationship between ferroptotic cell death and immune response demonstrated by recent studies enlightened us to detect the underlying roles of ferroptosis-related long noncoding RNAs (frlncRNAs) in the tumor microenvironment of bladder cancer (BCa). We collected 121 ferroptosis regulators from previous studies. Based on their expression values, 408 cases with BCa were clustered. The patients in different clusters showed diverse immune infiltration, immunotherapy response, and chemotherapy effectiveness, revalidating the tight correlation with ferroptosis and tumor immunity. Through differential, coexpression, Kaplan-Meier, Lasso, and Cox analysis, we developed a 22-lncRNA-pair signature to predict the prognosis of BCa based on gene-pair strategy, where there is no need for definite expression values. The areas under the curves are all over 0.8. The risk model also helped to predict immune infiltration, immunotherapeutic outcomes, and chemotherapy sensitivity. Totally, the prognostic assessment model indicated a promising predictive value, also providing clues for the interaction between ferroptosis and BCa immunity. [ABSTRACT FROM AUTHOR]

Background: Epithelial ovarian cancer (EOC), as a lethal malignancy in women, is often diagnosed as advanced stages. In contrast, intermediating between benign and malignant tumors, ovarian low malignant potential (LMP) tumors show a good prognosis. However, the differential diagnosis of the two diseases is not ideal, resulting in delays or unnecessary therapies. Therefore, unveiling the molecular differences between LMP and EOC may contribute to differential diagnosis and novel therapeutic and preventive policies development for EOC. Methods: In this study, three microarray data (GSE9899, GSE57477 and GSE27651) were used to explore the differentially expressed genes (DEGs) between LMP and EOC samples. Then, 5 genes were screened by protein–protein interaction (PPI) network, receiver operating characteristic (ROC), survival and Pearson correlation analysis. Meanwhile, chemical-core gene network construction was performed to identify the potential drugs or risk factors for EOC based on 5 core genes. Finally, we also identified the potential function of the 5 genes for EOC through pathway analysis. Results: Two hundred thirty-four DEGs were successfully screened, including 81 up-regulated genes and 153 down-regulated genes. Then, 5 core genes (CCNB1, KIF20A, ASPM, AURKA, and KIF23) were identified through PPI network analysis, ROC analysis, survival and Pearson correlation analysis, which show better diagnostic efficiency and higher prognostic value for EOC. Furthermore, NetworkAnalyst was used to identify top 15 chemicals that link with the 5 core genes. Among them, 11 chemicals were potential drugs and 4 chemicals were risk factors for EOC. Finally, we found that all 5 core genes mainly regulate EOC development via the cell cycle pathway by the bioinformatic analysis. Conclusion: Based on an integrated bioinformatic analysis, we identified potential biomarkers, risk factors and drugs for EOC, which may help to provide new ideas for EOC diagnosis, condition appraisal, prevention and treatment in future. [ABSTRACT FROM AUTHOR]

Background: Whether the change of the pre- and postoperative systemic inflammatory response (SIR) levels will affect the prognosis of gastric cancer (GC) is unclear. We aimed to investigate the dynamic changes in the pre- and postoperative SIR and their prognostic value for GC. Methods: The clinicopathological data from 2257 patients who underwent radical gastrectomy between January 2009 and December 2014 at Fujian Medical University Union Hospital (FMUUH) were analyzed. Perioperative SIR changes were reported as changes in the lymphocyte-monocyte ratio (LMR), neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and systemic immune-inflammation index (SII). Results: The SIR levels showed different trends from postoperative months 1 to 12. Multivariate analysis showed that preoperative (pre)-LMR was an independent predictor for the prognosis (P = 0.024). The postoperative 12-month (post-12-month) LMR predicted the 5-year overall survival (OS) rate with the highest accuracy (areas under the curve [AUC] 0.717). Patients were divided into four groups according to the optimal cutoff of the preoperative and post-12-month LMR: high pre-LMR to high postoperative (post)-LMR group, high pre-LMR to low post-LMR group, low pre-LMR to high post-LMR group, and low pre-LMR to low post-LMR group. The survival analysis showed 5-year OS rate was significantly higher in patients with high post-12-month LMR than in patients with low post-12-month LMR, regardless of pre-LMR levels (81.6% vs. 44.2%, P < 0.001). The prognostic accuracy was significantly improved by incorporating the post-12-month LMR in the tumor-node-metastasis (TNM) staging system (P = 0.003). Conclusions: The remeasurement of LMR at post-12-month is helpful in predicting the long-term survival of GC. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the effects of three nutritional scoring systems: Prognostic Nutritional Index (PNI), Controlling Nutritional Status (CONUT), and Naples Prognostic Score (NPS) on the short- or long-term prognosis of gastric cancer (GC) patients who underwent radical gastrectomy.Methods: The clinicopathological data of 2182 patients who underwent radical gastrectomy at the Fujian Medical University Union Hospital (FMUUH) from 2009 to 2014 were retrospectively analyzed. The effects of the PNI, CONUT, and NPS on the short- or long-term prognosis of GC patients were analyzed.Results: Overall, 359 (16.5%) patients had postoperative complications. There was no significant association between the PNI, CONUT, and NPS and postoperative complications (P > 0.05); however, high CONUT and NPS were significantly associated with severe postoperative complications (P < 0.05). Univariate analysis showed that PNI, CONUT, and NPS were all associated with overall survival (OS) (P < 0.001). However, multivariate analysis showed that only PNI was an independent risk factor for OS (P = 0.004), and the 5-year OS rate in the low PNI group was significantly lower than that in the normal PNI group (55.5% vs 75.4%, P < 0.05). The area under the curve (AUC) and the c-index of PNI were significantly higher than those of CONUT and NPS. The prognostic efficiency of combining PNI and TNM stage was also significantly better than that of TNM staging alone (P < 0.05).Conclusion: The current study demonstrated that CONUT and NPS are important for assessing the risk of severe postoperative complications. However, PNI is an independent risk factor for the long-term prognosis of GC patients who underwent radical gastrectomy and can improve the prognostic efficiency of TNM staging. [ABSTRACT FROM AUTHOR]

Background: In clinical practice, carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 are the most common markers measured before and after surgery for gastric cancer (GC). However, which pre- or post-operative combined tumour markers (CEA and CA19-9) have more prognostic value remains unclear.Methods: Consecutive patients undergoing a resection for GC at the Fujian Medical University Union Hospital were included as a discovery database between January 2011 and December 2014. The prognostic impact of pre- and post-operative tumour markers was evaluated using Kaplan-Meier log-rank survival analysis and multivariable Cox regression analysis. The results were then externally validated.Results: A total of 735 and 400 patients were identified in the discovery cohort and in the validation cohort, respectively. Overall survival rates decreased in a stepwise manner in association with the number of pre- and post-operative positive tumour markers (both P < 0.001). Multivariable analysis revealed that the number of pre-operative positive tumour markers was an independent prognostic factor (P < 0.05). For patients with abnormal pre-operative tumour markers, normalisation of tumour markers after surgery is an independent prognostic protective factor (hazard ratio (HR) = 0.618; 95% confidence interval (CI) = 0.414-0.921), and patients with both positive post-operative tumour markers had double the risk of overall death (HR = 2.338; 95% CI = 1.071-5.101). Similar results were observed in the internal validation and external validation cohorts.Conclusion: Pre-operative tumour markers have a better discriminatory ability for post-operative survival in GC patients than post-operative tumour markers, and the normalisation of tumour markers after surgery was associated with better survival. [ABSTRACT FROM AUTHOR]

Background: We sought to investigate the prognostic value of complete blood count (CBC)-based biomarkers for patients with resectable gastric cancer (GC).Methods: Patients with GC who underwent primary surgical resection between December 2008 and December 2013 were included. The estimated area under the curve (AUC) and multivariate Cox regression models were used to identify the best CBC-based biomarker. Time-dependent receiver operating characteristic (t-ROC) curve analysis was used to predict overall survival and compare the prognostic impact.Results: In the 1810 patients analyzed, the median follow-up period was 51.0 months (range 1-101 months). Based on multivariate analysis, the lymphocyte-monocyte ratio (LMR) and hemoglobin (Hb) level were independent prognostic factors (both P < 0.05). Based on the LMR and Hb level, we established the CBC-based inflammatory score (CBCS). A higher CBCS was associated with older age, female sex, higher American Society of Anesthesiologists (ASA) score, proximal tumor location, larger tumor size, later stage and vascular involvement (all P < 0.05). Univariate analyses showed that a higher CBCS was also associated with worse overall survival (OS), which was consistent in each stage (all P < 0.05). Multivariate analysis revealed that the CBCS was a significant independent biomarker (P < 0.05). The AUC for the CBCS (0.627) was significantly higher than the AUCs for the LMR (0.573) and Hb level (0.605) (both P < 0.05). Furthermore, the t-ROC curve of the CBCS was superior to that of the prognostic nutritional index (PNI), systemic immune-inflammation index (SII), modified Glasgow prognostic score (mGPS) and C-reactive protein/albumin ratio (CRP/Alb) throughout the observation period.Conclusion: The preoperative LMR and Hb level were optimal CBC-based biomarkers for predicting OS in GC patients after curative resection. Based on the LMR and Hb, we developed a novel and easily obtainable prognostic score called the CBCS, which may improve the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Object: Glioma is a common malignant tumours in the central nervous system (CNS), that exhibits high morbidity, a low cure rate, and a high recurrence rate. Currently, immune cells are increasingly known to play roles in the suppression of tumourigenesis, progression and tumour growth in many tumours. Therefore, given this increasing evidence, we explored the levels of some immune cell genes for predicting the prognosis of patients with glioma.Methods: We extracted glioma data from The Cancer Genome Atlas (TCGA). Using the Cell-type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) algorithm, the relative proportions of 22 types of infiltrating immune cells were determined. In addition, the relationships between the scales of some immune cells and sex/age were also calculated by a series of analyses. A P-value was derived for the deconvolution of each sample, providing credibility for the data analysis (P < 0.05). All analyses were conducted using R version 3.5.2. Five-year overall survival (OS) also showed the effectiveness and prognostic value of each proportion of immune cells in glioma; a bar plot, correlation-based heatmap (corheatmap), and heatmap were used to represent the proportions of immune cells in each glioma sample.Results: In total, 703 transcriptomes from a clinical dataset of glioma patients were drawn from the TCGA database. The relative proportions of 22 types of infiltrating immune cells are presented in a bar plot and heatmap. In addition, we identified the levels of immune cells related to prognosis in patients with glioma. Activated dendritic cells (DCs), eosinophils, activated mast cells, monocytes and activated natural killer (NK) cells were positively related to prognosis in the patients with glioma; however, resting NK cells, CD8+ T cells, T follicular helper cells, gamma delta T cells and M0 macrophages were negatively related to prognosis in the patients with glioma. Specifically, the proportions of several immune cells were significantly related to patient age and sex. Furthermore, the level of M0 macrophages was significant in regard to interactions with other immune cells, including monocytes and gamma delta T cells, in glioma tissues through sample data analysis.Conclusion: We performed a novel gene expression-based study of the levels of immune cell subtypes and prognosis in glioma, which has potential clinical prognostic value for patients with glioma. [ABSTRACT FROM AUTHOR]

Background: Most lymph node metastasis (LNM) models for early gastric cancer (EGC) include lymphovascular invasion (LVI) as a predictor. However, LVI must be confirmed by postoperative pathology. In this study, we aimed to develop a model for predicting the risk of LNM/LVI in EGC using preoperative factors.Methods: EGC patients who underwent radical gastrectomy at Fujian Medical University Union Hospital and Sun Yat-sen University Cancer Center (n = 1460) were selected as the training set. The risk factors of LNM/LVI were investigated. Data from the International study group on Minimally Invasive surgery for GASTRIc Cancer trial (n = 172) were selected as the validation set.Results: In the training set, the incidence of LNM/LVI was 21.6%. The 5-year cancer-specific survival rates of patients with and without LNM/LVI were 92.4 and 95.0%, respectively, with significant difference (P = 0.030). Multivariable logistic regression analysis showed that the four independent risk factors for LNM/LVI were female, tumor larger than 20 mm, submucosal invasion and undifferentiated tumor histological type (all P <  0.05); the area under the curve (AUC) was 0.694 (95% confidence interval [CI]: 0.659-0.730). Patients were divided into low-risk, intermediate-risk, high-risk and extremely high-risk groups by recursive partitioning analysis; the incidences of LNM/LVI were 5.4, 12.6, 24.2 and 37.8%, respectively (P <  0.001). The AUC of the validation set was 0.796 (95%CI, 0.662-0.851) and the predictive performance of the LNM/LVI risk in the validation set was consistent with that in the training set.Conclusions: The risk of LNM/LVI in differentiated mucosal EGC is low, which indicated that endoscopic resection is a treatment option. The risk of LNM/LVI in undifferentiated mucosal EGC and submucosa EGC are high and gastrectomy with lymph node dissection is suggested. [ABSTRACT FROM AUTHOR]

The time to platelet recovery (TPR) is becoming a predicting factor during the treatment of childhood acute leukaemia. However, the initial pre-treatment platelet count (PPC) could interfere with TPR. Here, we integrated both TPR and PPC as the average daily platelet amount increase (Ap) to predict the prognosis in childhood B-ALL during the recovery period.148 patients were enrolled. The relationship between the Ap and MRD was evaluated, and Multivariate analysis was performed to evaluate whether Ap was independently associated with a better EFS. The PPC was inversely correlated with TPR (rs = −0.519, P = 0.021). Patients in Ap >3.9 × 109/L group had better EFS (x2 = 3.109, P = 0.028) than TPR ≤ 16d. Multivariate analysis indicated that Ap > 3.9 × 109/L was independently associated with a longer EFS (RR = 3.468; 95%CI: 1.037–11.597, P = 0.043). However, when introducing both MRD and Ap > 3.9 × 109/L as candidate variables, the Ap > 3.9 × 109/L lost its independent effect (P = 0.081). The strong association between MRD on treatment day 33 and Ap > 3.9 × 109/L (x2 = 148.00, P = 0.000) was responsible for this phenomenon. Ap could be a valuable prognostic indicator in childhood B-ALL. [ABSTRACT FROM AUTHOR]

Background: Association between several single‐nucleotide polymorphisms (SNPs) and breast cancer risk has been identified through genome‐wide association studies (GWAS), but little is known about their significance in patients' prognosis. We screened SNPs which were related to the prognosis of breast cancer in Henan Han population, analyzed relevant genes by bioinformatics in database, and further constructed the genetic regulatory network involved in the pathogenesis of breast cancer. Methods: We evaluated five SNPs in 232 cases of breast cancer at the Affiliated Tumor Hospital of Zhengzhou University. Relationships between five SNPs, clinical prognostic indicators, and disease‐free survival (DFS) were evaluated by Kaplan–Meier analysis and Cox proportional hazards model. Gene ontology (GO) functional annotation and Kyoto Encyclopedia of genes and Genome (KEGG) analysis were carried out to preliminarily establish genetic regulation network model of breast cancer. Bayesian algorithm was used to optimize the model. Results: The multivariate Cox proportional hazards model confirmed that SNP rs3803662 (TOX3/TNRC9) had correlation with DFS independently. In the multivariate Cox proportional hazards model, compared with GA/AA, GG increased the recurrent risk of breast cancer (p = .021, hazard ratio [HR] = 2.914). GO analysis showed that the function of TOX3/TNRC9 included biological_process, molecular_function, and cellular_component. According to KEGG signaling pathway database, the map of breast cancer‐related gene regulatory network was obtained. IGF‐IGF1R‐PI3K‐Akt‐mTOR‐S6K was the best possible pathway for the differentiation of breast cancer cells in this network and ER‐TOX3/TNRC9 was the best possible pathway for the survival of tumor cells in this network by Bayesian theorem optimization. Conclusions: SNP rs3803662 (TOX3/TNRC9) is an independent prognostic factor for breast cancer in Henan Han Population. ER‐TOX3/TNRC9 is the best possible pathway involved in the pathogenesis of breast cancer. [ABSTRACT FROM AUTHOR]

Background. Tumor immunotherapy and immunological checkpoint-related proteins are research hotspots. Intensity-modulated radiotherapy (IMRT) is the main treatment for nasopharyngeal carcinoma (NPC). Hence, the evaluation of its effect is very important. The aim of this study was to assess the relationship between the concentrations of soluble checkpoint proteins, plasma EBV-DNA, and cytokines in NPC patients treated with IMRT. Methods. In this study, the plasma samples of 37 NPC patients and 40 healthy controls were collected. Luminex MAGPIX was used to detect the concentrations of 32 plasma targets, including soluble programmed cell death 1 (sPD-1). RT-qPCR was used to measure EBV-DNA. Results. The concentrations of 33 plasma targets were detected in NPC patients before and after IMRT to explore the changes after IMRT. The results showed that IMRT could increase the expression of sPD-1 and significantly reduce the level of EBV-DNA in the plasma of NPC patients. The expression level of sPD-1 in TNM I/II patients was significantly higher than that in III/IV patients. Besides, the concentrations of 12 other targets were significantly different after IMRT, including LAG-3, PD-L1, TIM-3, IFN-γ, IL-12p70, IL-1β, IL-5, IL-6, TNF-α, IL-10, IL-17A, and IL-22. High sPD-1 patients had longer survival than those with low sPD-1. Also, patients with lower EBV-DNA and TNM grades I and II/III had longer survival than those with higher EBV-DNA or TNM IV. Conclusions. This study demonstrated that the concentration of sPD-1 was significantly increased and EBV-DNA was significantly reduced in the NPC patients after IMRT. Plasma EBV-DNA level was a highly specific and sensitive biomarker for NPC diagnosis. Both sPD-1 expression and EBV-DNA concentration in plasma were related to the survival of patients. [ABSTRACT FROM AUTHOR]

Background: The objective of the study was to investigate the effects of intra-abdominal infection after curative gastrectomy on the prognosis of patients. Patients and Methods: Data were collected for enrolled patients who underwent curative gastrectomy in two centers; the relationship between intra-abdominal infection and prognosis was analyzed. Results: Of the 5,721 patients in the entire group, intra-abdominal infection occurred in 202 (3.5%) patients. Co-morbidities and duration of surgical procedures ≥240 minutes represented the independent risk factors for intra-abdominal infection. The overall five-year survival of patients with and without intra-abdominal infection was 60.2% and 64.3%, respectively (p = 0.041). After propensity score matching, the five-year overall survival between the two groups was not significantly different (p = 0.909). T staging, N staging, American Society of Anesthesiologists score, and age were independent prognostic factors for the overall survival of patients who underwent curative gastrectomy. The meta-analysis of the random effects model showed that there were no significant differences in the five-year overall survival between patients with and without intra-abdominal infection. Conclusions: The development of intra-abdominal infection after curative gastrectomy is associated closely with co-morbidities and longer operation time, whereas intra-abdominal infection does not lead to reduced long-term survival of patients. [ABSTRACT FROM AUTHOR]

Background: Circulating tumor cells (CTCs) and relevant autophagy Beclin-1 genes expression are critical biomarkers for tumorigenesis and tumor progress. Here we investigated the relationship of dynamic changes of CTCs and Beclin-1 expression of CTCs with renal cell carcinoma (RCC) prognosis. Materials and methods: A total of 69 patients with RCC were enrolled and divided into two groups based on the postoperative status of distant metastasis, including metastasis-free group (n = 58) and metastatic group (n = 11). Demographic characteristics of each patient were recorded in detail. All 69 enrolled patients had received multiple CTC tests and peripheral blood samples were obtained at three different time points (1 day before operation, 6 months and 12 months after operation). Peripheral blood samples were drawn before each time point and CTCs were separated by using Can Patrol CTC enrichment technique. CTCs were divided into epithelial, mesenchymal and mixed phenotype based on different surface biomarkers. RNA in situ hybridization assay was used to detect the expression of Beclin1 gene. Results: The percentages of epithelial, mesenchymal and mixed CTCs were 11.64%, 28.04% and 60.32%, respectively. There were no significant differences of initial CTCs counts between metastasis-free group (8.43 ± 5.15) and metastatic group (7.71 ± 3.82) (P > 0.05). As for metastatic group, the number of mixed CTCs at 12 months postoperatively was significantly higher than that of mixed CTCs preoperatively and 6 months postoperatively (P < 0.05). In the metastatic group, the number of Beclin1 positive CTCs was significantly higher than that of Beclin1 negative CTCs preoperatively (P < 0.05), moreover, there were several significantly changes of Beclin1 positive CTCs with different types and at different time points. Conclusion: The recurrence or metastasis of RCC was uncorrelated with initial CTCs counts, but probably related with the variation trend of CTCs, especially mesenchymal CTCs and Beclin1 positive CTCs. [ABSTRACT FROM AUTHOR]

Background: This study sought to explore whether lymphovascular invasion can affect the prognosis of patients with stage N0 gastric cancer and to evaluate the survival benefit of adjuvant chemotherapy for such patients.Method: From January 2006 to December 2011, a total of 2102 gastric cancer patients undergoing radical gastric resection were enrolled in this study. Homogeneity, discriminatory ability, and monotonicity of gradients in the combination of lymphovascular invasion and the 8th edition of the AJCC staging system and the 8th edition of the AJCC staging system alone were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. The Kaplan-Meier method and the log-rank test were used to analyze between-group differences in survival rate.Result: The median follow-up time of the whole group was 58 months, and the average age of the whole group was 63.9 years (range 21-89 years). The 3-year and 5-year overall survival rates in N0 patients with lymphovascular invasion were lower than those in N0 patients without lymphovascular invasion (3-year OS: 78.3% vs 92.5%, 5-year OS: 70.0% vs 88.3%, p < 0.001). A multivariate analysis showed that age (p < 0.001), lymphovascular invasion (p < 0.001), and pT (p < 0.001) were independent risk factors for the prognosis of N0 patients. Compared with the 8th edition of the AJCC staging system alone, the 8th AJCC staging system combined with lymphovascular invasion demonstrated a better linear trend χ2, likelihood ratio χ2 statistics, and AIC value (68.99 vs 58.58, 70.18 vs 58.36, 1473.38 vs 1485.04). In pT3N0M0 patients with lymphovascular invasion, the 3-year and 5-year overall survival rates of the adjuvant chemotherapy group were higher than those of the surgery alone group (3-year OS: 83.3% vs 68.2%, 5-year OS: 72.3% vs 50.0%, p = 0.048).Conclusion: Lymphovascular invasion is an independent prognostic factor in N0 patients. The 8th AJCC staging system combined with lymphovascular invasion can improve the accuracy of the AJCC staging system for N0 patients. Moreover, adjuvant chemotherapy improves the survival of pT3N0M0 patients with lymphovascular invasion. [ABSTRACT FROM AUTHOR]

Background: The systemic inflammation score (SIS), based on preoperative serum albumin (Alb) level and lymphocyte-to-monocyte ratio (LMR), has been shown to be a novel prognostic score for some tumors. We investigate the prognostic value of the SIS in patients with resectable gastric cancer (GC).Methods: Patients with GC who underwent curative resection between December 2008 and December 2013 were included. Time-dependent receiver operating characteristics analysis (t-ROC), concordance index (C-index) and AUC were used to compare the prognostic impact.Results: Totally, 1786 patients with resectable GC were included in the study. By multivariate analysis, the SIS was not an independent prognostic factor. However, the normal Alb level (≥ 40 g/l) and LMR ≥ 3.4 both remained independent protective factors for GC (both P < 0.05). Due to the similar survival of patients with LMR ≥ 3.4 and LMR < 3.4 in the normal Alb group, we combined the two subgroups to establish the modified SIS (mSIS). Multivariate analysis revealed that the mSIS was the only significant independent biomarker (P < 0.05). The t-ROC curve and C-index for the mSIS were superior to those of the SIS throughout the observation period. Furthermore, the AUC of the mSIS was significantly greater than that of the SIS at 3 and 5 years after operation (both P < 0.05).Conclusion: The preoperative mSIS is a novel, simple and useful prognostic factor for postoperative survival in patients with GC and can be used as a part of the preoperative risk stratification process to improve the prediction of clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: To determine whether laparoscopic surgery can be used in high-risk patients with gastric cancer.Methods: The clinicopathological data of 3743 patients with primary gastric adenocarcinoma, collected from January 2007 to December 2014, were retrospectively analyzed. Patients who had ≥ 1 of the following conditions were defined as high-risk patients: (1) age ≥ 80 years; (2) BMI ≥ 30 kg/m2; (3) ASA (American Society of Anesthesiologists) grade ≥ 3; or (4) clinical T stage 4 (cT4). Propensity score matching (PSM) was used to reduce confounding bias; then, we compared the short-term and long-term efficacy of laparoscopic gastrectomy (LG) with open gastrectomy (OG) in high-risk patients with gastric cancer.Results: A total of 1296 patients were included in PSM. After PSM, no significant difference in clinicopathological data was observed between the LG group (n = 341) and the OG group (n = 341). The operative time (181.70 vs. 266.71 min, p < 0.001) and blood loss during the operation (68.11 vs. 225.54 ml, p < 0.001) in the LG group were significantly lower than those in the OG group. In the LG and OG groups, postoperative complications occurred in 39 (11.4%) and 63 (18.5%) patients, respectively, p = 0.010. Multivariate analysis showed that laparoscopic surgery was an independent protective factor against postoperative complications (p = 0.019). The number of risk factors was an independent risk factor for postoperative complications (p = 0.021). The 5-year overall survival rate in the LG group was comparable to that in the OG group (55.0 vs. 52.0%, p = 0.086). Hierarchical analysis further confirmed that the LG and OG groups exhibited comparable survival rates among patients with stages cI, pI, cII, pII, cIII, and pIII (all p > 0.05).Conclusions: For high-risk patients with gastric cancer, LG not only exhibits better short-term efficacy than OG but also has a comparable 5-year survival rate to OG. [ABSTRACT FROM AUTHOR]

Background or Purpose: This study was designed to determine the value of AJCC staging 7th edition and improved AJCC staging in assessing the prognosis of gastric neuroendocrine carcinoma (GNEC).Methods: In total, GNEC 475 patients in the Surveillance, Epidemiology, and End Results (SEER) database and 129 GNEC patients in our department undergoing resection were included. The former served as the test group, and the latter served as the validation group. Those with stage IIIb disease were allocated into four subgroups, and improved AJCC staging was established. The AIC and C indices were used to evaluate the capacities of different TNM staging.Results: Significant overlap between stages IIIb and IIIa in both the test and validation groups was found. In the test group, T staging and age at disease diagnosis were independent prognostic factors for patients with stage IIIb. Stage IIIb was divided into T1N1, T2N1, T3N1 and T4N1, and the improved AJCC staging-mTNM staging was created. In mTNM staging, the IIIb survival curve did not cross those of stages IIIa and IIb, which had a smaller AIC (2490 vs. 2507) value and larger C index (0.7624 vs. 0.7450, P = 0.228). Similar results were obtained for the validation group.Conclusion: T stage was an independent factor influencing the prognosis of stage IIIb GNEC patients, and the improved AJCC staging proposed here has good prognostic value. [ABSTRACT FROM AUTHOR]

Abstract Background Long non-coding RNAs (lncRNAs) can be used as prognostic biomarkers in many types of cancer. Objective We sought to establish an lncRNA signature to improve postoperative risk stratification for patients with localized clear cell renal cell carcinoma (ccRCC). Design, setting, and participants Based on the RNA-seq data of 444 stage I–III ccRCC tumours from The Cancer Genome Atlas project, we built a four-lncRNA-based classifier using the least absolute shrinkage and selection operation (LASSO) Cox regression model in 222 randomly selected samples (training set) and validated the classifier in the remaining 222 samples (internal validation set). We confirmed this classifier in an external validation set of 88 patients with stage I–III ccRCC from a Japan cohort and using quantitative reverse transcription polymerase chain reaction (RT-PCR) in another three independent sets that included 1869 patients from China with stage I–III ccRCC. Outcome measurements and statistical analysis Univariable and multivariable Cox regression, Harrell's concordance index (c-index), and time-dependent receiver operating characteristic curves were used to evaluate the association of the classifier with overall survival, disease-specific survival, and disease-free survival. Results and limitations Using the LASSO Cox regression model, we built a classifier named RCClnc4 based on four lncRNAs: ENSG00000255774, ENSG00000248323, ENSG00000260911, and ENSG00000231666. In the RNA-seq and RT-PCR data sets, the RCClnc4 signature significantly stratified patients into high-risk versus low-risk groups in terms of clinical outcome across and within subpopulations and remained as an independent prognostic factor in multivariate analyses (hazard ratio range, 1.34 [95% confidence interval {CI}: 1.03–1.75; p = 0.028] to 1.89 [95% CI, 1.55–2.31; p < 0.001]) after adjusting for clinical and pathologic factors. The RCClnc4 signature achieved a higher accuracy (mean c-index, 0.72) than clinical staging systems such as TNM (mean c-index, 0.62) and the stage, size, grade, and necrosis (SSIGN) score (mean c-index, 0.64), currently reported prognostic signatures and biomarkers for the estimation of survival. When integrated with clinical characteristics, the composite clinical and lncRNA signature showed improved prognostic accuracy in all data sets (TNM + RCClnc4 mean c-index, 0.75; SSIGN + RCClnc4 score mean c-index, 0.75). The RCClnc4 classifier was able to identify a clinically significant number of both high-risk stage I and low-risk stage II–III patients. Conclusions The RCClnc4 classifier is a promising and potential prognostic tool in predicting the survival of patients with stage I–III ccRCC. Combining the lncRNA classifier with clinical and pathological parameters allows for accurate risk assessment in guiding clinical management. Patient summary The RCClnc4 classifier could facilitate patient management and treatment decisions. Take Home Message Our RCClnc4 classifier could add prognostic value to existing clinicopathological risk factors for stage I–III clear cell renal cell carcinoma and provide a more accurate and individualized risk assessment beyond reported signature. The RCClnc4 classifier may facilitate patient management and treatment decisions. [ABSTRACT FROM AUTHOR]

Background: To assess the prognostic factors and investigate the optimal treatment of gastric mixed adenoneuroendocrine tumors.Methods: We retrospectively analyzed clinical data from 80 patients with gastric mixed adenoneuroendocrine carcinoma that received radical resection in our department from January 2007 to December 2016. Risk factors for relapse and survival were analyzed using a multivariate Cox proportional hazards regression model. Gastric mixed adenoneuroendocrine carcinoma was divided into neuroendocrine carcinoma and adenocarcinoma based on the predominant type in the tumor.Results: The 3-year overall survival was 40% in the neuroendocrine carcinoma group and 75% in the adenocarcinoma group (P = 0.006). The neuroendocrine carcinoma (NEC)-dominant tumors and a Ki-67-positive index ≥60% were independent risk factors for worse overall survival. The 3-year recurrence-free survival was 33% in the neuroendocrine carcinoma group and 68% in the adenocarcinoma group. NEC-dominant tumors and a Ki-67-positive index ≥60% were independent risk factors for gastric mixed adenoneuroendocrine carcinoma recurrence. Patients in the adenocarcinoma group that received adjuvant chemotherapy exhibited significantly better overall survival than patients that did not receive chemotherapy (median survival time 43 months vs. 13 months, P = 0.026).Conclusion: The NEC-dominant tumors and a Ki-67-positive index ≥60% were significantly associated with worse survival and a higher recurrence rate for gastric mixed adenoneuroendocrine carcinoma patients. Patients in the adenocarcinoma group may benefit from gastric adenocarcinoma treatments. [ABSTRACT FROM AUTHOR]

The aims of this study were to examine the levels of serum and exosomal miR-137, miR-155 and miR-223, three neuroinflammation-related miRNAs, in dementia patients and to explore the value of these miRNAs for the diagnosis and prognostic evaluation of dementia. Thirty-two patients with dementia were enrolled, and sixteen volunteers without dementia served as controls. Serum exosomes were isolated by precipitation with ExoQuick and characterized by western blotting, nanoparticle-tracking analysis and immunofluorescence microscopy. The levels of both total serum miRNAs and serum exosomal miRNAs were determined by real-time quantitative PCR. Total serum miRNAs and serum exosomal miRNAs were both detected to be down-regulated. The median level of serum exosomal miR-223 was significantly decreased in dementia patients ( p  < 0.01). The level of miR-223 was significantly correlated with Mini-Mental State Examination (MMSE) scores, Clinical Dementia Rating (CDR) scores, magnetic resonance spectroscopy (MRS) spectral ratios and serum concentrations of IL-1β, IL-6, TNF-α, and CRP. The diagnostic utility of exosomal miR-233 was evaluated by the area under the receiver operating characteristic (ROC) curve, and the area under the curve (AUC) was 0.875. This study suggests that serum exosomal miR-223 is a promising biomarker for diagnosing dementia and evaluating the progression of disease. [ABSTRACT FROM AUTHOR]

We investigated the impact of minimal residual disease (MRD) obtained from different approaches on the outcomes of 141 B lymphoblastic leukemia (B-ALL) patients. Among 169 samples with more than 5% blasts by morphology, 3.6% (6/169) were Flow-MRD negative. Of the 212 positive molecular-MRD samples from Ph+ ALL patients, 55 (25.9%) were Flow-MRD negative. Before consolidation or allogeneic stem cell transplantation (allo-HSCT), negative Flow-MRD was associated with improved survival (p = .019 and.041, respectively) for Ph− ALL patients, but not for Ph+ ALL (p = .111 and.812, respectively). There was no difference in overall survival (OS) by achievement of complete molecular response at complete remission (CR, p = .333 and.863, respectively). Our results indicated that the results of MRDs detected with different methods varied. Flow-MRD can be used as a reliable prognostic marker for Ph− ALL patients. MRD either by flow cytometry or quantitative reverse transcription-polymerase chain reaction (qRT-PCR) at CR did not affect OS or DFS for Ph+ ALL. [ABSTRACT FROM AUTHOR]