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Abstract Background Identifying lymph node metastasis areas during surgery for early invasive lung adenocarcinoma remains challenging. The aim of this study was to develop a nomogram mathematical model before the end of surgery for predicting lymph node metastasis in patients with early invasive lung adenocarcinoma. Methods In this study, we included patients with invasive lung adenocarcinoma measuring ≤ 2 cm who underwent pulmonary resection with definite pathology at Qilu Hospital of Shandong University from January 2020 to January 2022. Preoperative biomarker results, clinical features, and computed tomography characteristics were collected. The enrolled patients were randomized into a training cohort and a validation cohort in a 7:3 ratio. The training cohort was used to construct the predictive model, while the validation cohort was used to test the model independently. Univariate and multivariate logistic regression analyses were performed to identify independent risk factors. The prediction model and nomogram were established based on the independent risk factors. Recipient operating characteristic (ROC) curves were used to assess the discrimination ability of the model. Calibration capability was assessed using the Hosmer–Lemeshow test and calibration curves. The clinical utility of the nomogram was assessed using decision curve analysis (DCA). Results The overall incidence of lymph node metastasis was 13.23% (61/461). Six indicators were finally determined to be independently associated with lymph node metastasis. These six indicators were: age (P

Abstract Background More and more studies have demonstrated that potassium channel tetramerization domain-containing 5 (KCTD5) plays an important role in the development of cancer, but there is a lack of comprehensive research on the biological function of this protein in pan-cancer. This study systematically analyzed the expression landscape of KCTD5 in terms of its correlations with tumor prognosis, the immune microenvironment, programmed cell death, and drug sensitivity. Methods We investigated a number of databases, including TCGA, GEPIA2, HPA, TISIDB, PrognoScan, GSCA, CellMiner, and TIMER2.0. The study evaluated the expression of KCTD5 in human tumors, as well as its prognostic value and its association with genomic alterations, the immune microenvironment, tumor-associated fibroblasts, functional enrichment analysis, and anticancer drug sensitivity. Real-time quantitative PCR and flow cytometry analysis were performed to determine the biological functions of KCTD5 in lung adenocarcinoma cells. Results The results indicated that KCTD5 is highly expressed in most cancers and that its expression is significantly correlated with tumor prognosis. Moreover, KCTD5 expression was related to the immune microenvironment, infiltration by cancer-associated fibroblasts, and the expression of immune-related genes. Functional enrichment analysis revealed that KCTD5 is associated with apoptosis, necroptosis, and other types of programmed cell death. In vitro experiments showed that knockdown of KCTD5 promoted apoptosis of A549 cells. Correlation analysis confirmed that KCTD5 was positively correlated with the expression of the anti-apoptotic genes Bcl-xL and Mcl-1. Additionally, KCTD5 was significantly associated with sensitivity to multiple antitumor drugs. Conclusion Our results suggest that KCTD5 is a potential molecular biomarker that can be used to predict patient prognosis, immunoreactions and drug sensitivity in pan-cancer. KCTD5 plays an important role in regulating programmed cell death, especially apoptosis.

Abstract Background Abnormal expression of long non-coding RNA (lncRNA) FTX (five prime to Xist), which is involved in X chromosome inactivation, has been reported in various tumors. However, the effect of FTX on the development of pancreatic cancer (PC) has not been elucidated. The purpose of this study was to explore the possible molecular mechanism of FTX in PC. Methods Quantitative real-time PCR (qRT-PCR) was used to measure the expression levels of FTX and miR-513b-5p in PC cell lines. Proliferation and apoptosis of PC cells were determined by CCK-8, Edu assay, and flow cytometry. Invasion and migration ability of PC cells were detected by Transwell assay and scratch test. Bioinformatics analysis, luciferase reporter gene assay, and RNA immunoprecipitation (RIP) assay were used to verify the direct binding between FTX and miR-513b-5p. The xenotransplantation mouse model was established to explore the effect of FTX and miR-513b-5p on the PC tumor growth in vivo. Results The expression levels of FTX were increased in PC cell lines, and silencing of FTX remarkably suppressed the invasion ability and cell viability. Besides, FTX could bind to miR-513b-5p as a competitive endogenous RNA, thus promoting the invasion and proliferation ability of PC cells. Moreover, knockdown of FTX inhibited the tumor growth and increased the expression levels of miR-513b-5p and apoptosis-related proteins in vivo. Conclusions FTX could directly combine with miR-513b-5p as a competitive endogenous RNA, thus promoting the occurrence and development of PC in vitro and in vivo.

Abstract Background Performance of urinary cytology is recommended as the part of a standard diagnostic workup and base surveillance regimens in upper tract urothelial carcinoma (UTUC). However, the effect of positive voided urine cytology (VUC) on UTUC prognosis, compared with negative VUC, has not been fully demonstrated. This study aimed to evaluate the impact of preoperative VUC on predicting intravesical recurrence, disease recurrence, and mortality in patients with UTUC who underwent nephroureterectomy (RNU). Methods Clinicopathological information was collected from 315 UTUC patients treated with RNU. The association between VUC and oncological outcomes was analyzed using the Kaplan–Meier method with log-rank test and Cox proportional hazards regression models. Multiple logistic regression analysis was performed to identify the influence of VUC on tumor grade. Results Preoperative positive VUC, presenting in 101 patients (32%), was significantly associated with tumor multifocality (P = 0.017) and higher tumor grade (P = 0.010). On multivariable Cox regression analyses, preoperative positive VUC was an independent prognostic factor of intravesical recurrence-free survival (RFS) (hazard ratio [HR] = 2.21, 95% confidence interval [CI] 1.06–4.64; P = 0.035), RFS (HR = 1.80, 95% CI 1.08–2.99; P = 0.023), and cancer-specific survival (CSS) (HR = 1.87, 95% CI 1.10–3.18; P = 0.020), but not overall survival (HR = 1.32, 95% CI 0.80–2.18; P = 0.28). Logistic regression analysis revealed that VUC was related to high tumor grade in UTUC (odds ratio = 2.23, 95%CI 1.15–4.52). Conclusion Preoperative positive VUC significantly increases the risk of intravesical recurrence in UTUC patients undergoing RNU. In addition, positive VUC is an adverse predictor of RFS and CSS, which might be due to the association between positive VUC and high tumor grade.

Background: The standard treatment for esthesioneuroblastoma, a rare malignant nasal vault neoplasm, is not established.Methods: We retrospectively assessed the clinicopathological features, prognostic factors and treatment methods for 187 patients with esthesioneuroblastoma treated in China between 1981 and 2015. Overall survival (OS) and disease-free survival (DFS) were evaluated using the Kaplan-Meier method and log-rank tests.Results: Twenty-three (12.3%), 48 (25.7%) and 113 (60.4%) patients had Kadish stage A, B and C esthesioneuroblastoma; 3 (1.6%) had unknown stage. Overall, 117 (62.6%) patients received surgery and combined radiotherapy with or without chemotherapy; 35 (18.7%) received radiotherapy with or without chemotherapy; 32 (17.1%) received surgery alone; and 3 (1.6%) received palliative treatment. Three-year OS and DFS for the entire cohort were 66.7% and 57.5%, respectively. Three-year OS for stage A, B and C were 91.3%, 91.2% and 49.5% (P < 0.0001). Three-year OS was 16.7% and 66.7% for patients with and without distant metastasis (P < 0.0001). Surgery and combined radiotherapy with or without chemotherapy led to better OS and DFS than other treatment modes (both P < 0.0001). Univariate and multivariate analysis showed distant metastasis (hazard ratio [HR] = 2.162, 95% confidence interval [CI] = 1.145, 4.082, P = 0.017) and not receiving a combined modality treatment (HR = 2.391, 95% CI = 1.356, 4.218, P = 0.003) were independent prognostic factors for poor OS and DFS.Conclusions: This study indicates surgery and combined radiotherapy may currently be the optimal treatment for esthesioneuroblastoma. [ABSTRACT FROM AUTHOR]

Background: Transforming growth factor-beta (TGF-β) is associated with a higher incidence of distant metastasis and decreased survival. Whether TGF-β can be used as a prognostic indicator of colorectal cancer (CRC) remains controversial.Methods: The Medline, EMBASE and Cochrane databases were searched from their inception to March 2016. The studies that focused on TGF-β as a prognostic factor in patients with CRC were included in this analysis. Overall survival (OS) and disease-free survival (DFS) were analysed separately. A meta-analysis was performed, and hazard ratios (HR) with 95% confidence intervals (CI) were calculated.Results: Twelve studies were included in the analysis, of which 8 were used for OS and 7 for DFS. In all, 1622 patients with CRC undergoing surgery were included. Combined HRs suggested that high expression of TGF-β had a favourable impact on OS (HR = 1.68, 95% CI: 1.10-2.59) and DFS (HR = 1.11, 95% CI: 1.03-1.19) in CRC patients. For OS, the combined HRs of Asian studies and Western studies were 1.50 (95% CI: 0.61-3.68) and 1.80 (95% CI: 1.33-2.45), respectively. For DFS, the combined HRs of Asian studies and Western studies were 1.42 (95% CI: 0.61-3.31) and 1.11 (95% CI: 1.03-1.20), respectively.Conclusions: This meta-analysis demonstrates that TGF-β can be used as a prognostic biomarker for CRC patients undergoing surgery, especially for CRC patients from Western countries. [ABSTRACT FROM AUTHOR]

Background: Due to the uncommon nature of primary spinal epidural lymphomas (PSELs), there has been little research looking at prognostic indicators for the tumor. To our knowledge, this is the largest study to evaluate possible clinical and pathologic prognostic factors in PSEL patients.Methods: We retrospectively reviewed 130 cases of PSEL, including 36 Chinese patients and 94 published case reports from 1985 to 2015. Patient treatment regimens included surgery (S; n = 119), surgery followed by chemotherapy (S + CT; n = 25), surgery followed by radiotherapy (S + RT; n = 26), and surgery followed by chemotherapy and radiotherapy (S + CT + RT; n = 50).Results: Review of the most recent case follow-up data (time varied) found 51 patients (47%) alive and tumor-free, 10 patients (9%) alive with tumor present, and 47 patients (44%) deceased. The 3-year overall survival (OS) and disease-free survival (DFS) rates were 81.1% and 46.3%, respectively. Favorable prognostic factors found by univariate analysis were female sex, B-cell lymphoma diagnosis, cervical spine location, and combined modality treatment. Furthermore, multivariate analysis revealed that thoracic spine location (HR = 4.629, 95% CI = [1.911, 31.667], P = 0.042 for OS) and the lack of combined modality treatment (HR = 12.697, 95% CI = [2.664, 48.612], P < 0.0001 for DFS) were associated with poor survival in PSEL patients.Conclusions: PSEL demonstrates specific clinical features and is associated with a relatively good prognosis. Thoracic spine location is a significant poor prognostic factor, and combined modality treatment is associated with improved disease-free survival, but not overall survival. [ABSTRACT FROM AUTHOR]

Background: In South and Southeast Asian, the majority of buccal squamous cell carcinoma (BSCC) can arise from oral submucous fibrosis (OSF). BSCCs develop in OSF that are often not completely resected, causing local relapse. The aim of our study was to find candidate protein biomarkers to detect OSF and predict prognosis in BSCCs by quantitative proteomics approaches.Methods: We compared normal oral mucosa (NBM) and paired biopsies of BSCC and OSF by quantitative proteomics using isobaric tags for relative and absolute quantification (iTRAQ) to discover proteins with differential expression. Gene Ontology and KEGG networks were analyzed. The prognostic value of biomarkers was evaluated in 94 BSCCs accompanied with OSF. Significant associations were assessed by Kaplan-Meier survival and Cox-proportional hazards analysis.Results: In total 30 proteins were identified with significantly different expression (false discovery rate < 0.05) among three tissues. Two consistently upregulated proteins, ANXA4 and FLNA, were validated. The disease-free survival was negatively associated with the expression of ANXA4 (hazard ratio, 3.4; P = 0.000), FLNA (hazard ratio, 2.1; P = 0.000) and their combination (hazard ratio, 8.8; P = 0.002) in BSCCs.Conclusion: The present study indicates that iTRAQ quantitative proteomics analysis for tissues of BSCC and OSF is a reliable strategy. A significantly up-regulated ANXA4 and FLNA could be not only candidate biomarkers for BSCC prognosis but also potential targets for its therapy. [ABSTRACT FROM AUTHOR]

Background: Hemostatic alterations occur during the development of cancer. Plasma D-dimer is a hypercoagulability and fibrinolytic system marker that is increased in patients with various solid tumours. The aim of this study was to evaluate the hemostatic status of nasopharyngeal carcinoma (NPC) patients by assessing plasma D-dimer levels to investigate its value as a prognostic marker. Methods: We retrospectively analysed 717 patients with nasopharyngeal carcinoma, and we applied Cox regression and log-rank tests to assess the association of D-dimer levels with disease-free survival (DFS), distant metastasis-free survival (DMFS), and overall survival (OS). D-dimer levels were measured using a quantitative D-dimer latex agglutination assay. Results: Using the 3rd quartile values (0.8 µg/L) as the optimal cut-offs, we found that patients with high D-dimer levels have a shorter 3-year DFS, (79%, 95%CI (73.1-84.9)) vs. (69%, 95%CI (59.2-78.8)), DMFS (87%, 95%CI (83.1-90.9)) vs. (77%, 95%CI (69.2-84.8)), and overall survival (82%, 95%CI (76.1-87.9)) vs. (76%, 95%CI (66.2-85.8)). Multivariate analysis revealed that pre-treatment D-dimer levels and EBV DNA were significant independent factors for DFS, DMFS, and OS in NPC patients. Subgroup analyses indicated that the plasma D-dimer levels could effectively stratify patient prognosis for early cancer, advanced stage cancer, and patients with EBV DNA =4000 copies/ml. Conclusions: High D-dimer levels were associated with poor disease-free survival, distant metastasis-free survival, overall survival, and increased risk of mortality in NPC patients. Prospective trials are required to assess the prognostic value of D-dimer levels. [ABSTRACT FROM AUTHOR]

Background: Elevated serum YKL-40 levels have been observed in various cancers. We evaluated the diagnostic performance of serum YKL-40 alone or in combination with the CEA, CYFRA21-1 and SCCA tumor markers for patients with esophageal squamous cell carcinoma (ESCC). Methods: YKL-40 was detected in ESCC cell lines and tissues by real-time RT-PCR, Western blotting and ELISA. YKL-40 protein expression was determined in 20 ESCC tumor tissues using immunohistochemistry. Serum YKL-40 was measured by ELISA in 126 healthy donors, 59 patients with benign esophageal diseases and 150 patients with ESCC. Serum CEA, CYFRA21-1 and SCCA were determined by electrochemiluminescence. Results: YKL-40 mRNA and protein were observed in ESCC cancer cell lines, tissues and cell culture media, respectively. YKL-40 expression was observed in 17 of 20 ESCC samples (85%). Serum YKL-40 concentration was significantly elevated in patients with ESCC (Range: 6.95-502.10 ng/ml) compared with patients with benign diseases (Range: 1.21-429.30 ng/ml; P = 0.038) and healthy controls (Range: 2.56-132.26 ng/ml; P < 0.001). ROC curves demonstrated that serum YKL-40 has a sensitivity of 72.70%, a specificity of 84.13% and an AUC of 0.874 for the diagnosis of ESCC, which was superior to CEA (Sen: 8.00%; Spe: 96.80%, AUC = 0.652), CYFRA21-1 (Sen: 40.00%; Spe: 92.06%, AUC = 0.746) and SCCA (Sen: 32.67%; Spe: 94.44%, AUC = 0.789). The YKL-40 and SCCA combination was better for diagnosing ESCC (Sen: 82.00%, Spe: 79.37%, PPV: 82.55 and NPV: 78.74; AUC = 0.917) than the YKL-40 and CEA combination (Sen: 74.00%, Spe: 83.20%, PPV: 84.09 and NPV: 72.73; AUC = 0.877), the YKL-40 and CYFRA21-1 combination (Sen: 82.00%, Spe: 77.78%, PPV: 81.46% and NPV: 78.40%; AUC = 0.897) or the CEA, CYFRA21-1 and SCCA combination (Sen: 56.67%, Spe: 84.80%, PPV: 81.73 and NPV: 61.99; AUC = 0.831). Associations between serum YKL-40 levels and the clinic characteristics of ESCC were not significant, with the exception of age (p = 0.001). Conclusions: ESCC tumor cells and tissues express YKL-40. Serum YKL-40 may be a potential biomarker for ESCC. Serum YKL-40 in combination with SCCA significantly increases the sensitivity of detecting ESCC. [ABSTRACT FROM AUTHOR]

Background: Gastric cancer is the second leading cause of cancer death and remains a major clinical challenge due to poor prognosis and limited treatment options. Long noncoding RNAs (lncRNAs) have emerged recently as major players in tumor biology and may be used for cancer diagnosis, prognosis, and potential therapeutic targets. Although downregulation of lncRNA GAS5 (Growth Arrest-Specific Transcript) in several cancers has been studied, its role in gastric cancer remains unknown. Our studies were designed to investigate the expression, biological role and clinical significance of GAS5 in gastric cancer. Methods: Expression of GAS5 was analyzed in 89 gastric cancer tissues and five gastric cancer cell lines by quantitative reverse-transcription polymerase chain reaction (qRT-PCR). Over-expression and RNA interference (RNAi) approaches were used to investigate the biological functions of GAS5. The effect of GAS5 on proliferation was evaluated by MTT and colony formation assays, and cell apoptosis was evaluated by hochest stainning. Gastric cancer cells transfected with pCDNA3.1-GAS5 were injected into nude mice to study the effect of GAS5 on tumorigenesis in vivo. Protein levels of GAS5 targets were determined by western blot analysis. Differences between groups were tested for significance using Student's t-test (two-tailed). Results: We found that GAS5 expression was markedly downregulated in gastric cancer tissues, and associated with larger tumor size and advanced pathologic stage. Patients with low GAS5 expression level had poorer disease-free survival (DFS; P = 0.001) and overall survival (OS; P < 0.001) than those with high GAS5 expression. Further multivariable Cox regression analysis suggested that decreased GAS5 was an independent prognostic indicator for this disease (P = 0.006, HR = 0.412; 95%CI = 2.218-0.766). Moreover, ectopic expression of GAS5 was demonstrated to decrease gastric cancer cell proliferation and induce apoptosis in vitro and in vivo, while downregulation of endogenous GAS5 could promote cell proliferation. Finally, we found that GAS5 could influence gastric cancer cells proliferation, partly via regulating E2F1 and P21 expression. Conclusion: Our study presents that GAS5 is significantly downregulated in gastric cancer tissues and may represent a new marker of poor prognosis and a potential therapeutic target for gastric cancer intervention. [ABSTRACT FROM AUTHOR]

Background: Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is a multifunctional Ig-like cell adhesion molecule that has a wide range of biological functions. According to previous reports, serum CEACAM1 is dysregulated in different malignant tumours and associated with tumour progression. However, the serum CEACAM1 expression in non-small-cell lung carcinomas (NSCLC) is unclear. The different expression ratio of CEACAM1-S and CEACAM1-L isoform has seldom been investigated in NSCLC. This research is intended to study the serum CEACAM1 and the ratio of CEACAM1-S/L isoforms in NSCLC. Methods: The expression of the serum CEACAM1 was determined by enzyme-linked immunosorbent assay. The protein expression and the location of CEACAM1 in tumours were observed by immunohistochemical staining. The CEACAM1 mRNA levels in tumour and normal adjacent tissues were measured using quantitative real-time PCR, and the expression patterns and the rate of CEACAM1-S and CEACAM1-L were analysed by reverse transcription-PCR. Results: Serum CEACAM1 levels were significantly higher in NSCLC patients compared with that from normal healthy controls (P <0.0001). 17 patients (81%) among 21 showed high expression of CEACAM1 by immunohistochemical staining. Although no significant differences were found between tumour and normal tissues on mRNA expression levels of CEACAM1 (P >0.05), the CEACAM1-S and the CEACAM1-S/L (S: L) ratios were significantly higher in tumour than normal tissues (P <0.05). Conclusions: Our data indicated that the serum levels of CEACAM1 could discriminate lung cancer patients from health donors and that CEACAM1 might be a useful marker in early diagnosis of NSCLC. Moreover, our results showed that the expression patterns of CEACAM1 isoforms could be changed during oncogenesis, even when total CEACAM1 in tumour tissues did not show significant changes. Our study suggested that the expression ratios of CEACAM1-S/ CEACAM1-L might be a better diagnostic indicator in NSCLC than the quantitative changes of CEACAM1 [ABSTRACT FROM AUTHOR]

Background: Gallbladder cancer is the most common billiary tract malignancy and carries a very poor prognosis. Somatostatin was recently shown to play an important role in the development of various tumors. In the current study, we evaluated the effect of doxorubicin on the chemosensitivity of gallbladder cancer cells and xenograft growth after treatment with somatostatin. Methods: Twenty-four hours after somatostatin treatment, doxorubicin was gradually added and the growth curve of gallbladder cancer cells was determined. Exponential-phase gallbladder cancer cells were treated with doxorubicine or co-treated with doxorubicine and somastatine and the respective IC50 values were determined. In addition, the inhibitory effect on the growth of gallbladder cancer xenograft on nude mice was evaluated using the same treatments as those described above. Results: Treatment of gallbladder cancer cells with somatostatin led to a block in the cell cycle at the S phase. Growth inhibition of gallbladder cancer cells by doxorubicin was concentration-dependent (P < 0.05). However, upon co-treatment with doxorubicin and somatostatin, the IC50 value significantly decreased as compared to that of cells treated with doxorubicine alone (P < 0.05). Interestingly, treatment with either doxorubicin or somatostatin did not significantly inhibit xenograft growth on nude mice, in contrast to a co-treatment with both drugs (P < 0.05). Conclusion: Somatostatin most likely sensitizes the chemotherapeutic effect and diminishes the cytotoxicity of doxorubicin in a gallbladder cancer cell line and in mouse gallbladder cancer xenografts. [ABSTRACT FROM AUTHOR]

Abstract Background Porphyromonas gingivalis plays an oncogenic role in development and progression of esophageal squamous cell carcinoma (ESCC). However, the impact of P. gingivalis on local recurrence of early ESCC or precancerous lesion after ESD treatment remains unknown. The present study aimed to evaluate the impact of P. gingivalis on local recurrence after ESD treatment of early ESCC or high-grade dysplasia (HGD). Methods The amount of P. gingivalis was assessed by immunohistochemistry in 205 patients with early ESCC or HGD. Univariate and multivariate Cox regression analyses were performed to determine the effect of P. gingivalis on local recurrence. Propensity score matching analysis was performed to reduce the imbalance of baseline characteristics. A nomogram integrating significant prognostic factors was built for local recurrence prediction. Results The amount of P. gingivalis increased significantly in neoplasms that invaded up to muscularis mucosa and submucosa compared with lesions confined to epithelium or lamina propria. Overabundance of P. gingivalis was positively associated with invasion depth, post-ESD stricture and local recurrence. Univariate and multivariate Cox regression analyses revealed that P. gingivalis, longitudinal length of lesion and lymphovascular invasion were independent predictors for post-ESD recurrence. A nomogram comprising P. gingivalis, lymphovascular involvement, and lesion length performed well for prediction of post-ESD local recurrence with the concordance indices of 0.72 (95%CI, 0.62 to 0.80), 0.72 (95%CI, 0.63 to 0.80), and 0.74 (95%CI, 0.65 to 0.83) in the validation cohort, the entire cohort, and the subcohort after PSM, respectively. Conclusion P. gingivalis overabundance is a risk factor and a potential predictor for local recurrence of early ESCC or HGD after ESD treatment. Thus, clearance of P. gingivalis represents an attractive strategy for prognosis improvement and for prevention of ESCC.