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Immunogenic cell death (ICD) is a newly discovered form of cellular demise that triggers adaptive immune responses mediated by T cells. However, the immunogenic cell death-related lncRNAs (ICDRLs) involved in bladder cancer (BC) development and progression remain to be further elucidated. Molecular profiling data and clinicopathological information for BC patients were obtained from TCGA, and the ICDRGs list was obtained from published literature. For the identification of ICDRLs, Pearson co-expression analysis was performed, and a prognostic signature based on 13 ICDRLs was constructed by univariate assays and LASSO assays. Herein, an ICDRLSig consisting of 13 ICDRLs was constructed. KM curves and ROC curves demonstrated that the constructed signature in the TCGA training, testing, entire and external sets have good predictive performance. Multivariate assays illuminated that the signature is an independent predictor for BC patients' OS, exhibiting greater predictive power for the survival than traditional clinicopathological features. Additionally, patients in the high-ICDRLSig risk subgroup had more abundant immune infiltration, higher immune checkpoint gene expression, lower TMB and poorer response to immunotherapy. We have developed a novel ICDRLSig that can be exploited for survival prediction and provide a reference for further individualized treatment. [ABSTRACT FROM AUTHOR]

Bladder cancer (BLCA) is one of the most frequent urothelium carcinoma, but with poor prognosis due to lack of reliable predictive biomarkers. Metabolic reprogramming involving in various nutrients, and is reported to be closely associated with malignant progression in BLCA. With the use of transcriptome sequencing data profiles of 349 patients from The Cancer Genome Atlas, we established a three-gene glycolysis-related signature to predict the prognosis of BLCA patients. Our signature constructed on the basis of AK3, GALK1 and NUP205 expression, detail features and interactions between these three genes were further explored. We established a nomogram by integrating clinical variables and the risk score. Glycolytic level and proliferation ability were detected to study the role and mechanisms of NUP205 on BLCA. The connections between three genes in our signature were independent. We found our signature gains more value for patients with highly malignant stage. The established nomogram also confirmed that the signature had a eligible clinically predict capacity. After inhibited NUP205 expression, we found the glycolysis level of BLCA cells decreased and proliferation ability suppressed, mainly through AMPK signaling pathway inactivation. Collectively, our study explored a three-gene glycolysis-related signature that predict the prognosis of patients with BLCA, and highlights NUP205 as a potential therapeutic target for inhibiting glycolytic processes and proliferation in BLCA cells. [ABSTRACT FROM AUTHOR]

The study aims to search and identify differentially expressed genes (DEGs) in cervical cancer tissues as novel biomarkers to predict cervical cancer prognosis. The Cancer Genome Atlas (TCGA) data on gene expression profiles in cervical cancer were downloaded and analyzed using R software to identify DEGs in cervical cancer tissues. miRNAs targeted by differentially expressed long non-coding RNAs (DElncRNAs) and mRNAs targeted by microRNAs (miRNAs) were identified using the online miRcode, miRTarBase, TargetScan, and miRDB tools. The ceRNA network and lncRNA expression modules in cervical cancer tissues were constructed using weighted gene co-expression network analysis (WGCNA) and analyzed bioinformatically. The Kaplan–Meier analysis was performed to confirm these DEGs as prognostic markers. Immunohistochemical (IHC) analysis was used to verify expression of the hub genes in 10 paired cervical cancer and normal tissues. A total of 1914 DEmRNAs, 210 DElncRNAs, and 67 DEmiRNAs were identified in cervical cancer samples. There were 39 lncRNAs, 19 miRNAs, and 87 mRNAs involved in the ceRNA network and 25 DElncRNAs, three DEmiRNAs, and four mRNAs involved in the ceRNA sub-network. CACNA1C-AS1 was associated with the yellow and blue modules in the ceRNA sub-network, and LIFR-AS1 was associated with the blue module. The DEmRNAs were involved in cancer-related pathways, and three hub genes (i.e., E2F1, CCNB1, and CCNE1) were highly expressed in cervical squamous cell carcinoma and adenocarcinoma tissues and associated with the prognosis of patients. The ceRNA network and WGCNA analyses are useful to identify novel DEGs that can serve as prognostic markers in cervical cancer. The DEGs will be validated in future studies. [ABSTRACT FROM AUTHOR]

Purpose: The Chromobox (CBX) family proteins are crucial elements of the epigenetic regulatory machinery and play a significant role in the development and advancement of cancer. Nevertheless, there is limited understanding regarding the role of CBXs in development or progression of prostate cancer (PCa). Our objective is to develop a unique prognostic model associated with CBXs to improve the accuracy of predicting outcomes of patients with PCa. Methods: Data from TCGA and GEO databases were analyzed to assess differential expression, prognostic value, gene pathway enrichment, and immune cell infiltration. COX regression analysis was utilized to identify the independent prognostic factors that impact disease-free survival (DFS). The expression of CBX2 and FOXP3+ cells infiltration was verified by immunohistochemical staining of clinical tissue sections. In vitro proliferation, migration and invasion assay were conducted to examine the function of CBX2. RNA-seq was employed to examine the CBX2 related pathway enrichment. Results: CBX2, CBX3, CBX4, and CBX8 were upregulated, while CBX6 and CBX7 were downregulated in PCa tissues. CBXs expression varied by stage and grade. Elevated expression of CBX1, CBX2, CBX3, CBX4 and CBX8 is correlated with poor outcome. CBX2 expression, T stage, and Gleason score were independent prognostic factors. The expression level of CBX2 in PCa tissues was significantly higher than that in adjacent normal tissues. More Treg infiltration was observed in the group with high CBX2 expression. CBX2 expression affected PCa cell growth, migration, and invasion. Conclusions: CBX2 is involved in the development and advancement of PCa, suggesting its potential as a reliable prognostic indicator for PCa patients. [ABSTRACT FROM AUTHOR]

Additional chromosomal abnormalities(ACAs) at diagnosis are associated with inferior prognosis in chronic myeloid leukemia. However, the prognostic significance of ACAs in adult patients with Philadelphia Chromosome Positive acute lymphoblastic leukemia (Ph + ALL) receiving TKI-targeted drugs and allogeneic hematopoietic stem cell transplantation(HSCT) is unknown. One hundred thirty-six adult patients with Ph + ALL were included in the study and retrospectively analysed, evaluating the effect of ACAs on outcomes of transplantation. ACAs are observed in 60 cases (44%). ACAs detected in more than 5% of cases were defined as major-route and encompass: +der(22), +der(9), + 8, -7 and complex karyotype. The median follow-up was 26.4 months. In the subgroup analyses of major route ACAs, three-year cumulative incidence of relapse (CIR) and progression-free survival(PFS) are statistically significant in + 8[66.7% vs.23.7%, P = 0.024; 77.8% vs. 23.7%, P = 0.0087], -7[53.8% vs. 23.7%, P = 0.035%; 61.5% vs. 32.9%, P = 0.033], and complex karyotypes[42.9% vs. 23.7%, P = 0.027; 47.6% vs. 23.7%] compared with t(9;22) sole. Additionally, the 3-year CIR for Ph + ALL with + der(22) is 44% vs. 23.7% for t(9;22) sole(P = 0.045). The 3-year overall survival (OS) in the − 7 group is 46.5%, which is statistically significant compared with the other groups(P = 0.001). In multivariate analyses, three years CIR and PFS are statistically significant in + der(22), + 8, -7 and complex karyotype compared with t(9;22) sole(P < 0.05). More importantly, Ph + ALL with − 7 was negatively associated with the rate of 3-year OS(P = 0.012). Thus, ACAs at diagnosis appear to have a significant prognostic impact on transplantation outcomes in patients with Ph + ALL. [ABSTRACT FROM AUTHOR]

Background: UNC5A had been reported to play crucial roles in multiple cancers. However, little was known about the associations among UNC5A and glioma. Therefore, we first combined scRNA-seq, proteomics, as well as bulk RNA-seq in order to investigate UNC5A's functions in gliomas. Methods: Online databases provided scRNA-seq, proteomics, as well as bulk RNA-seq data on UNC5A in gliomas. The following procedures were conducted in order: QRT-PCR, Norman chart, gene set enrichment analysis (GSEA), and univariate/multifactor Cox regression analyses. We further explored the associations among UNC5A and tumor immunity. Results: By comparing gliomas with normal tissues, the TCGA dataset showed a significantly reduced expression of UNC5A, which was also confirmed by GSE50161, GSE4290, and QRT-PCR findings (p < 0.05). In both the TCGA and CGGA datasets, gliomas patients with low-UNC5A expression would have poorer overall survival (OS) prognoses (p < 0.05). ScRNA-seq analysis by the CancerSEA online website presented that UNC5A had a low expression in various glioma clusters and significantly associated with six functional states. Moreover, UNC5A might be a reliable independent biomarker of OS in gliomas patients (p < 0.05). Based on the results of GSEA, UNC5A might be connected to three significant pathways in gliomas. We also successfully created a Norman chart to assess the OS prognoses of these patients. Additionally, in aspects of tumor immunity, the infiltration levels of immune cells in LGG, the immune cell pathways, tumor immune microenvironment, as well as immune checkpoints in both LGG and GBM were revealed to be significantly influenced by UNC5A (p < 0.05). Conclusions: UNC5A was found to have prognostic and immunological significance in gliomas, offering patients with gliomas new treatment options. [ABSTRACT FROM AUTHOR]

Objective: Our study aimed to assess the ability of high-sensitivity modified Glasgow prognostic Score (HS-mGPS) predicting survival in patients undergoing radical surgery for hepatocellular carcinoma (HCC) and to compare the impact with other Inflammation-Based prognostic scoring systems including Glasgow prognostic Score (GPS) and modified GPS (mGPS). Methods: Our study evaluated 293 patients with HCC who had undergone hepatectomy at the Third Affiliated Hospital of Soochow University between 2010 and 2018. The HS-mGPS, mGPS, and GPS were calculated based on particular cut-off values of preoperative C-reactive protein and albumin, and the correlations between HS-mGPS and clinicopathological parameters were evaluated. Univariate and multivariate survival analyses were conducted by Kaplan–Meier method and Cox proportional hazards model. To evaluate the discrimination ability of each prognostic score, the receiver operating characteristic (ROC) curve were generated and the areas under the curve (AUC) were measured and compared. Result: The study results indicated a correlation between elevated HS-mGPS scores and adverse clinical factors, including higher BCLC stage, C-P grade, multiple tumors, and larger tumor diameter. Kaplan-Meier and univariate survival analyses revealed that higher scores of HS-mGPS, GPS, and mGPS were all associated with significantly reduced overall survival (OS) (all p < 0.001). In multivariate survival analysis, HS-mGPS emerged as an independent risk factor for poor OS in patients undergoing hepatectomy for HCC (p = 0.010), along with factors including maximal tumor diameter (p < 0.001), microvascular invasion (MVI) (p = 0.008), and BCLC stage (p = 0.001). The analysis of ROC curves and the AUC values indicated that HS-mGPS outperforms GPS and mGPS in predicting the long-term prognosis of patients with resectable HCC. Conclusion: Preoperative HS-mGPS proves superior in predicting adverse long-term outcomes in HCC patients undergoing radical surgery. [ABSTRACT FROM AUTHOR]

The relationship between blood urea nitrogen to albumin ratio (BAR) and the prognosis of patients with tuberculosis (TB) complicated by sepsis remains unclear. This study aimed to explore the association between BAR and overall patient prognosis. This was a retrospective cohort study of patients with TB complicated by sepsis who were admitted to the intensive care unit (ICU) of the Public Health Clinical Center of Chengdu between January 2019 and February 2023. The relationship between BAR values and prognosis in these patients was investigated using multivariate Cox regression, stratified analysis with interaction, restricted cubic spline (RCS), and threshold effect analysis. Sensitivity analyses were conducted to assess the robustness of the results. Our study included 537 TB patients complicated by sepsis admitted in the ICU, with a median age of 63.0 (48.0, 72.0) years; 76.7% of whom were men. The multivariate-restricted cubic spline analysis showed a non-linear association between BAR and patient prognosis. In the threshold analysis, we found that TB patients complicated by sepsis and a BAR < 7.916 mg/g had an adjusted hazard ratio (HR) for prognosis of 1.163 (95% CI 1.038–1.303; P = 0.009). However, when the BAR was ≥ 7.916 mg/g, there was no significant increase in the risk of death. The results of the sensitivity analysis were stable. [ABSTRACT FROM AUTHOR]

Purpose: IKAROS family zinc finger 3 (IKZF3) is an oncogene involved in different malignancies, particularly in the development and malignant progression of lymphocytes. However, IKZF3 amplification and clinical significance in gastric cancers (GCs) remain unexplored. Methods: We examined IKZF3 amplification status in 404 GCs with HER2 amplification status using tissue microarray (TMA) and fluorescence in situ hybridization (FISH) assays. Results: IKZF3 amplification was detected in 6.9% (28/404) of all GC patients, with higher rates in intestinal-type gastric cancer (IGC) (11.22%, 22/196) compared to other types (2.88%, 6/208). HER2 amplification was identified in 16.09% (65/404) of all GC patients, with higher rates in IGC (20.92%, 41/196) compared to other types (11.54%, 24/208). Co-amplification of IKZF3 and HER2 was detected in 8.16% (16/196) of IGC patients and in 2.40% (5/208) of other types. IKZF3 amplification showed significant correlation with IGC (P = 0.001) and HER2 amplification (P = 0.0001). IKZF3 amplification exhibited significantly worse disease-free survival (DFS) (P = 0.014) and overall survival (OS) (P = 0.018) in GC patients, particularly in IGC (DFS: P < 0.001; OS: P < 0.001), rather than other types. Cox regression analysis demonstrate IKZF3 amplification as an independent poor prognostic factor in all GCs (P = 0.006, P = 0.004 respectively) and in IGC patients, regardless of stages I-II or III-IV (P = 0.007, P = 0.004 respectively). On the other hand, HER2 amplification was significantly associated with worse DFS (P = 0.008) and OS (P = 0.01) in IGC patients, but not in all GCs and in multivariate analysis. Within the subset of patients with HER2 amplification, those also exhibiting IKZF3 amplification displayed potential poorer prognosis (P = 0.08, P = 0.11 respectively). Conclusion: IKZF3 amplification was detected in minority of GC patients, especially in IGC, and was an independent indicator of poor prognosis. Our study, for the first time, found the prognostic value of IKZF3 was superior to HER2 for GC patients. [ABSTRACT FROM AUTHOR]

Objective: This study was designed to investigate the clinical features, treatment modalities, and risk factors influencing neurological recovery in patients who underwent scoliosis correction with delayed postoperative neurological deficit (DPND). Methods: Three patients with DPND were identified from 2 central databases for descriptive analysis. Furthermore, all DPND cases were retrieved from the PubMed and Embase databases. Neurological function recovery was categorized into complete and incomplete recovery groups based on the American Spinal Injury Association (ASIA) impairment scale. Results: Two patients were classified as type 3, and one was classified as type 2 based on the MRI spinal cord classification. Intraoperative neurophysiological monitoring (IONM) was consistently negative throughout the corrective procedure, and intraoperative wake-up tests were normal. The average time to DPND development was 11.8 h (range, 4–18 h), and all three patients achieved complete recovery of neurological function after undergoing revision surgery. A total of 14 articles involving 31 patients were included in the literature review. The mean time to onset of DPND was found to be 25.2 h, and 85.3% (29/34) of patients experienced DPND within the first 48 h postoperatively, with the most common initial symptoms being decreased muscle strength and sensation (26 patients, 83.9%). Regarding neurological function recovery, 14 patients were able to reach ASIA grade E, while 14 patients were not able to reach ASIA grade E. Univariate analysis revealed that preoperative diagnosis (p = 0.004), operative duration (p = 0.017), intraoperative osteotomy method (p = 0.033), level of neurological deficit (p = 0.037) and deficit source (p = 0.0358) were significantly associated with neurological outcomes. Furthermore, multivariate regression analysis indicated a strong correlation between preoperative diagnosis (p = 0.003, OR, 68.633; 95% CI 4.299–1095.657) and neurological prognosis. Conclusion: Our findings indicate that spinal cord ischemic injury was a significant factor for patients experiencing DPND and distraction after corrective surgery may be a predisposing factor for spinal cord ischemia. Additionally, it is important to consider the possibility of DPND when limb numbness and decreased muscle strength occur within 48 h after corrective scoliosis surgery. Moreover, emergency surgical intervention is highly recommended for DPND caused by mechanical compression factors with a promising prognosis for neurological function, emphasizing the importance of taking into account preoperative orthopedic diagnoses when evaluating the potential for neurological recovery. [ABSTRACT FROM AUTHOR]

Purpose: To develop a model based on whole-liver radiomics features of pre-treatment enhanced MRI for predicting the prognosis of hepatocellular carcinoma (HCC) patients undergoing continued transarterial chemoembolization (TACE) after TACE-resistance. Materials and Methods: Data from 111 TACE-resistant HCC patients between January 2014 and March 2018 were retrospectively collected. At a ratio of 7:3, patients were randomly assigned to developing and validation cohorts. The whole-liver were manually segmented, and the radiomics signature was extracted. The tumor and liver radiomics score (TLrad-score) was calculated. Models were trained by machine learning algorithms and their predictive efficacies were compared. Results: Tumor stage, tumor burden, body mass index, alpha-fetoprotein, and vascular invasion were revealed as independent risk factors for survival. The model trained by Random Forest algorithms based on tumor burden, whole-liver radiomics signature, and clinical features had the highest predictive efficacy, with c-index values of 0.85 and 0.80 and areas under the ROC curve of 0.96 and 0.83 in the developing cohort and validation cohort, respectively. In the high-rad-score group (TLrad-score > − 0.34), the median overall survival (mOS) was significantly shorter than in the low-rad-score group (17 m vs. 37 m, p < 0.001). A shorter mOS was observed in patients with high tumor burden compared to those with low tumor burden (14 m vs. 29 m, p = 0.007). Conclusion: The combined radiomics model from whole-liver signatures may effectively predict survival for HCC patients continuing TACE after TACE refractoriness. The TLrad-score and tumor burden are potential prognostic markers for TACE therapy following TACE-resistance. [ABSTRACT FROM AUTHOR]

Aquaporin 4-immunoglobulin G (AQP4-IgG) specifically targets aquaporin 4 in approximately 80% of Neuromyelitis Optica Spectrum Disorder (NMOSD) cases. NMOSD is presently categorized as anti-AQP4-antibody (Ab) positive or negative based on AQP4-Ab presence. The association between antibody titers and patient prognosis remains unclear. Therefore, the present study explores the correlation between severe attacks and serum AQP4 Ab titers in patients with neuromyelitis optica spectrum disorder. Data were gathered retrospectively from 546 patients with NMOSD between September 1, 2009, and December 1, 2021. Patients were categorized based on their AQP4-Ab titers: AQP4 titer ≥ 1:320 were classified as the high-titer group, AQP4 (+ +), and AQP4 titer of ≤ 1:100 were classified as the low-titer group, AQP4 (+). Clinical characteristics and prognoses between the two groups were compared. Patients with AQP4 (+) exhibited few severe optic neuritis (SON) attacks (false discovery rate [FDR] corrected p < 0.001), a reduced percentage experiencing SON attacks, and a lower incidence of visual disability than patients with AQP4 (+ +). Patients with AQP4 (+ +) and AQP4 (+) NMOSD exhibited significant difference in annual recurrence rate (ARR) (FDR-corrected p < 0.001). The lower AQP4 Ab titer group demonstrated reduced susceptibility to severe relapse with conventional immunosuppressive agents and rituximab (RTX) than the higher titer group. No significant differences in sex, age at onset, coexisting connective tissue diseases, motor disability, or mortality rates were observed between the two groups. Higher AQP4 Ab titers correlated with increased disease severity and visual disability in patients with NMOSD. [ABSTRACT FROM AUTHOR]

Objectives: To predict the functional outcome of patients with intracerebral hemorrhage (ICH) using deep learning models based on computed tomography (CT) images. Methods: A retrospective, bi-center study of ICH patients was conducted. Firstly, a custom 3D convolutional model was built for predicting the functional outcome of ICH patients based on CT scans from randomly selected ICH patients in H training dataset collected from H hospital. Secondly, clinical data and radiological features were collected at admission and the Extreme Gradient Boosting (XGBoost) algorithm was used to establish a second model, named the XGBoost model. Finally, the Convolution model and XGBoost model were fused to build the third "Fusion model." Favorable outcome was defined as modified Rankin Scale score of 0–3 at discharge. The prognostic predictive accuracy of the three models was evaluated using an H test dataset and an external Y dataset, and compared with the performance of ICH score and ICH grading scale (ICH-GS). Results: A total of 604 patients with ICH were included in this study, of which 450 patients were in the H training dataset, 50 patients in the H test dataset, and 104 patients in the Y dataset. In the Y dataset, the areas under the curve (AUCs) of the Convolution model, XGBoost model, and Fusion model were 0.829, 0.871, and 0.905, respectively. The Fusion model prognostic performance exceeded that of ICH score and ICH-GS (p = 0.043 and p = 0.045, respectively). Conclusions: Deep learning models have good accuracy for predicting functional outcome of patients with spontaneous intracerebral hemorrhage. Clinical relevance statement: The proposed deep learning Fusion model may assist clinicians in predicting functional outcome and developing treatment strategies, thereby improving the survival and quality of life of patients with spontaneous intracerebral hemorrhage. Key Points: • Integrating clinical presentations, CT images, and radiological features to establish deep learning model for functional outcome prediction of patients with intracerebral hemorrhage. • Deep learning applied to CT images provides great help in prognosing functional outcome of intracerebral hemorrhage patients. • The developed deep learning model performs better than clinical prognostic scores in predicting functional outcome of patients with intracerebral hemorrhage. [ABSTRACT FROM AUTHOR]

Background: The 8th AJCC TNM staging for non-metastatic lymph node-positive colon adenocarcinoma patients(NMLP-CA) stages solely by lymph node status, irrespective of the positivity of tumor deposits (TD). This study uses machine learning and Cox regression to predict the prognostic value of tumor deposits in NMLP-CA. Methods: Patient data from the SEER registry (2010–2019) was used to develop CSS nomograms based on prognostic factors identified via multivariate Cox regression. Model performance was evaluated by c-index, dynamic calibration, and Schmid score. Shapley additive explanations (SHAP) were used to explain the selected models. Results: The study included 16,548 NMLP-CA patients, randomized 7:3 into training (n = 11,584) and test (n = 4964) sets. Multivariate Cox analysis identified TD, age, marital status, primary site, grade, pT stage, and pN stage as prognostic for cancer-specific survival (CSS). In the test set, the gradient boosting machine (GBM) model achieved the best C-index (0.733) for CSS prediction, while the Cox model and GAMBoost model optimized dynamic calibration(6.473) and Schmid score (0.285), respectively. TD ranked among the top 3 most important features in the models, with increasing predictive significance over time. Conclusions: Positive tumor deposit status confers worse prognosis in NMLP-CA patients. Tumor deposits may confer higher TNM staging. Furthermore, TD could play a more significant role in the staging system. [ABSTRACT FROM AUTHOR]

Objectives: The clinical decision-making regarding choosing surgery alone (SA) or surgery followed by postoperative adjuvant chemotherapy (SPOCT) in esophageal squamous cell carcinoma (ESCC) remains controversial. We aim to propose a pre-therapy PET/CT image-based deep learning approach to improve the survival benefit and clinical management of ESCC patients. Methods: This retrospective multicenter study included 837 ESCC patients from three institutions. Prognostic biomarkers integrating six networks were developed to build an ESCC prognosis (ESCCPro) model and predict the survival probability of ESCC patients treated with SA and SPOCT. Patients who did not undergo surgical resection were in a control group. Overall survival (OS) was the primary end-point event. The expected improvement in survival prognosis with the application of ESCCPro to assign treatment protocols was estimated by comparing the survival of patients in each subgroup. Seven clinicians with varying experience evaluated how ESCCPro performed in assisting clinical decision-making. Results: In this retrospective multicenter study, patients receiving SA had a median OS 9.2 months longer than controls. No significant differences in survival were found between SA patients with predicted poor outcomes and the controls (p > 0.05). It was estimated that if ESCCPro was used to determine SA and SPOCT eligibility, the median OS in the ESCCPro-recommended SA group and SPOCT group would have been 15.3 months and 24.9 months longer, respectively. In addition, ESCCPro also significantly improved prognosis accuracy, certainty, and the efficiency of clinical experts. Conclusion: ESCCPro assistance improved the survival benefit of ESCC patients and the clinical decision-making among the two treatment approaches. Critical relevance statement: The ESCCPro model for treatment decision-making is promising to improve overall survival in ESCC patients undergoing surgical resection and patients undergoing surgery followed by postoperative adjuvant chemotherapy. Key Points: ESCC is associated with a poor prognosis and unclear ideal treatments. ESCCPro predicts the survival of patients with ESCC and the expected benefit from SA. ESCCPro improves clinicians' stratification of patients' prognoses. [ABSTRACT FROM AUTHOR]

Background: The treatment of myeloid sarcoma (MS) is challenging and has not markedly improved patient prognosis. The introduction of venetoclax (VEN) has changed the treatment of MS, and venetoclax-based therapy has been described as very promising in several case reports. Methods: In this retrospective study, we analyzed the treatment outcomes of 14 patients with MS treated with venetoclax-based therapy at The First Affiliated Hospital of Xiamen University from January 2020 to October 2023 Results: The cohort consisted of 7 (50%) women and 7 (50%) men with an average age of 37.5 years. Four patients (28.6%) had isolated MS de novo, 2 (14.2%) were diagnosed synchronously with AML, and 8 (57.2%) had isolated extramedullary relapse. The most common sites for MS in our cohort were the skin and lung, followed by the spinal canal, soft tissue, bone and kidney. Five patients were affected at more than three sites. Nine patients received VEN in combination with azacytidine, and 5 patients received VEN in combination with other agents. The median number of venetoclax therapies administered was 2 cycles (range: 1–10 cycles). A response was observed in all patients included in the study, with 8 patients (57.2%) achieving a CR and 3 patients (21.4%) achieving a PR, corresponding to an ORR (including CR and PR) of 78.6%. The median follow-up time for all patients was 13 months (range 1–44 months), and the 1 year OS for all patients was 67.7%. Conclusions: Venetoclax-based therapy shows excellent efficacy and safety in MS patients in the "real world" at a single institution, and a corresponding prospective study is needed to verify this conclusion. [ABSTRACT FROM AUTHOR]

T lymphoblastic leukemia /lymphoma (T-ALL/LBL) is a rare and highly aggressive neoplasm of lymphoblasts. We evaluated 195 T-ALL/LBL adolescent and adult patients who received ALL-type chemotherapy alone (chemo,n = 72) or in combination with autologous hematopoietic stem cell transplantation(auto-HSCT,n = 23) or allogeneic hematopoietic stem cell transplantation(allo-HSCT,n = 100) from January 2006 to September 2020 in three Chinese medical centers. 167 (85.6%) patients achieved overall response (ORR) with 138 complete response (CR) patients (70.8%) and 29 partial response (PR) patients (14.8%). Until October 1, 2023, no difference was found in 5-year overall survival (5-OS) and 5-year progression free survival(5-PFS) between allo-HSCT and auto-HSCT (5-OS 57.9% vs. 36.7%, P = 0.139, 5-year PFS 49.4% vs. 28.6%, P = 0.078) for patients who achieved CR, for patients who achieved PR, allo-HSCT recipients had higher 5-OS compared with chemo alone recipients (5-OS 23.8% vs. 0, P = 0.042). For patients undergoing allo-HSCT, minimal residual disease (MRD) negative population showed better 5-OS survival compared with MRD positive patients (67.8% vs. 19.6%, p = 0.000). There were no significant differences between early T-cell precursor (ETP), NON-ETP patients with or without expression of one or more myeloid-associated or stem cell-associated (M/S+) markers (NON-ETP with M/S+, NON-ETP without M/S+) groups in allo-HSCT population for 5-OS. (62.9% vs. 54.5% vs.48.4%, P > 0.05). Notch mutations were more common in patients with non-relapsed/refractory disease than relapsed/refractory disease (χ² =4.293, P = 0.038). In conclusion, Allo-HSCT could be an effective consolidation therapy not just for patients with CR, but also for those who achieved PR. The prognosis is significantly improved by obtaining MRD negative prior to allogeneic transplantation. [ABSTRACT FROM AUTHOR]

Background: Cytokine storm is known to impact the prognosis of coronavirus disease 2019 (COVID-19), since pro-inflammatory cytokine variants are associated with cytokine storm. It is tempting to speculate that pro-inflammatory cytokines variants may impact COVID-19 outcomes by modulating cytokine storm. Here, we verified this hypothesis via a comprehensive analysis. Methods: PubMed, Cochrane Library, Central, CINAHL, and ClinicalTrials.gov were searched until December 15, 2023. Case–control or cohort studies that investigated the impacts of rs1800795 or rs1800629 on COVID-19 susceptibility, severity, mortality, IL-6, TNF-α, or CRP levels were included after an anonymous review by two independent reviewers and consultations of disagreement by a third independent reviewer. Results: 47 studies (8305 COVID-19 individuals and 17,846 non-COVID-19 individuals) were analyzed. The rs1800629 A allele (adenine at the −308 position of the promoter was encoded by the A allele) was associated with higher levels of tumor necrosis factor-α (TNF-α) and C-reactive protein (CRP). In contrast, the rs1800795 C allele (cytosine at the −174 position of the promoter was encoded by the C allele) was linked to higher levels of interleukin-6 (IL-6) and CRP. In addition, the A allele of rs1800629 increased the severity and mortality of COVID-19. However, the C allele of rs1800795 only increased COVID-19 susceptibility. Conclusions: rs1800629 and rs1800795 variants of pro-inflammatory cytokines have significant impacts on systemic inflammatory profile and COVID-19 clinical outcomes. rs1800629 may serve as a genetic marker for severe COVID-19. [ABSTRACT FROM AUTHOR]

Background: Neuroendocrine neoplasm is a rare cancer of head and neck. This study aimed to evaluate clinical features, treatment outcomes, and prognostic factors of neuroendocrine neoplasm of head and neck treated at a single institution. Methods: Between Nov 2000 and Nov 2021, ninety-three patients diagnosed with neuroendocrine neoplasms of head and neck treated at our institution were reviewed retrospectively. The initial treatments included chemotherapy (induction, adjuvant, or concurrent) combined with radiotherapy in 40 patients (C + RT group), surgery followed by post-operative RT in 34 (S + RT group), and surgery plus salvage therapy in 19 patients (S + Sa group). Results: The median follow-up time was 64.5 months. 5-year overall survival rate (OS), progression-free survival rate (PFS), loco-regional relapse-free survival free rate (LRRFS) and distant metastasis-free survival rate (DMFS) were 64.5%, 51.6%, 66.6%, and 62.1%, respectively. For stage I–II, the 5-year LRRFS for patients' treatment regimen with or without radiotherapy (C + RT and S + RT groups versus S + Sa group) was 75.0% versus 12.7% (p = 0.015) while for stage III–IV, the 5-year LRRFS was 77.8% versus 50.0% (p = 0.006). The 5-year DMFS values for patients with or without systemic therapy (C + RT group versus S + RT or S + Sa) were 71.2% and 51.5% (p = 0.075). 44 patients (47.3%) experienced treatment failure and distant metastasis was the main failure pattern. Conclusions: Radiotherapy improved local–regional control and played an important role in the management of HNNENs. The optimal treatment regimen for HNNENs remains the combination of local and systemic treatments. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of diabetes mellitus and its sequelae has been on the rise, and diabetic foot ulcer (DFU) is the leading cause of non-traumatic lower limb amputation globally. The rising occurrence and financial burden associated with DFU necessitate improved clinical assessment and treatment. Diabetes has been found to enhance the formation of neutrophil extracellular traps (NETs) by neutrophils, and excessive NETs have been implicated in tissue damage and impaired wound healing. However, there is as yet insufficient evidence to clarify the value of NETs in assessing and predicting outcomes of DFU. Methods: We designed this prospective study with three cohorts formed from type 2 diabetes mellitus (T2DM) patients with DFU (n = 200), newly diagnosed T2DM patients (n = 42), and healthy donors (n = 38). Serum levels of NETs were detected for all groups, and the prognostic value for DFU-related amputation was analyzed. Results: The results showed that serum NET levels of the DFU group were significantly higher than in the T2DM group (P < 0.05), which also had significantly elevated serum NET levels compared to healthy donors (P < 0.05). Multivariate Cox regression showed that serum NET levels, diabetic foot surgical history, and Wagner grade were the risk factors for amputation (P < 0.05), and these three variables also exhibited the highest coefficient values in additional Lasso Cox regression. For patients with DFU, Kaplan-Meier curves showed that high serum NET levels associated with higher amputation probability (HR = 0.19, P < 0.01) and ROC curve based on NET value showed good validity for amputation (AUC: 0.727, CI 0.651–0.803). Conclusion: Elevated serum NET levels serve as an easily accessible serological prognostic marker for assessing the risk of DFU-related amputation, thereby offering evaluation metrics for healthcare providers. Further investigations are necessary to understand the mechanisms driving this relationship. [ABSTRACT FROM AUTHOR]

Treatment of glioblastoma multiforme (GBM) remains challenging. Unraveling the orchestration of glutamine metabolism may provide a novel viewpoint on GBM therapy. The study presented a full and comprehensive comprehending of the glutamine metabolism atlas and heterogeneity in GBM for facilitating the development of a more effective therapeutic choice. Transcriptome data from large GBM cohorts were integrated in this study. A glutamine metabolism-based classification was established through consensus clustering approach, and a classifier by LASSO analysis was defined for differentiating the classification. Prognosis, signaling pathway activity, tumor microenvironment, and responses to immune checkpoint blockade (ICB) and small molecular drugs were characterized in each cluster. A combinational therapy of glutaminase inhibitor CB839 with dihydroartemisinin (DHA) was proposed, and the influence on glutamine metabolism, apoptosis, reactive oxygen species (ROS), and migration was measured in U251 and U373 cells. We discovered that GBM presented heterogeneous glutamine metabolism–based clusters, with unique survival outcomes, activity of signaling pathways, tumor microenvironment, and responses to ICB and small molecular compounds. In addition, the classifier could accurately differentiate the two clusters. Strikingly, the combinational therapy of CB839 with DHA synergistically attenuated glutamine metabolism, triggered apoptosis and ROS accumulation, and impaired migrative capacity in GBM cells, demonstrating the excellent preclinical efficacy. Altogether, our findings unveil the glutamine metabolism heterogeneity in GBM and propose an innovative combination therapy of CB839 with DHA for this malignant disease. [ABSTRACT FROM AUTHOR]

Enhancement of vascular remodeling in affected brain tissue is a novel therapy for acute ischemic stroke (AIS). However, conclusions regarding angiogenesis after AIS remain ambiguous. Vascular endothelial growth factor A (VEGFA) and VEGF receptor 2 (VEGFR2) are potent regulators of angiogenesis and vascular permeability. We aimed to investigate the association between VEGFA/VEGFR2 expression in the acute stage of stroke and prognosis of patients with AIS. We enrolled 120 patients with AIS within 24 h of stroke onset and 26 healthy controls. Plasma levels of VEGFA and VEGFR2 were measured by enzyme-linked immunosorbent assay (ELISA). The primary endpoint was an unfavorable outcome defined as a modified Rankin Scale (mRS) score > 2 at 3 months after AIS. Univariate and multivariate logistic regression analyses were used to identify risk factors affecting prognosis. Plasma VEGFA and VEGFR2 were significantly higher in patients with AIS than in health controls, and also significantly higher in patients with unfavorable than those with favorable outcomes. Moreover, both VEGFA and VEGFR2 showed a significantly positive correlation with mRS at 3 months. Univariate and multivariate analyses showed VEGFA and VEGFR2 remained associated with unfavorable outcomes, and adding VEGFA and VEGFR2 to the clinical model significantly improved risk reclassification (continuous net reclassification improvement, 105.71%; integrated discrimination improvement, 23.45%). The new risk model curve exhibited a good fit with an area under the receiver operating characteristic curve (ROC) curve of 0.9166 (0.8658–0.9674). Plasma VEGFA and VEGFR2 are potential markers for predicting prognosis; thus these two plasma biomarkers may improve risk stratification in patients with AIS. [ABSTRACT FROM AUTHOR]

Background: Because of to the removal of subclassification of papillary renal cell carcinoma (pRCC), the survival prognostification of localized pRCC after surgical treatment became inadequate. Sarcopenia was widely evaluated and proved to be a predictive factor for prognosis in RCC patients. Therefore, we comprehensively investigated the survival prediction of the body composition parameters for localized pRCC. Methods: Patients pathologically diagnosed with pRCC between February 2012 and February 2022 in our center were enrolled. The body composition parameters, including skeletal muscle index (SMI), subcutaneous adipose tissue (SAT), and perirenal adipose tissue (PRAT), were measured by the images of preoperative computed tomography (CT). The primary outcome was set as progression-free survival (PFS), and the cutoff values of body composition parameters were calculated by using the Youden from receiver operating characteristic curve (ROC) curves. Univariate and multivariate Cox proportional regression analyses were performed to explore independent risk factors for survival prediction. Then, significant factors were used to construct a prognostic nomogram. The performance of the nomogram was evaluated by Harrell's C-index, calibration curves and time-dependent ROC curves. Results: A total of 105 patients were enrolled for analysis. With a median follow-up time of 30.48 months, 25 (23.81%) patients experienced cancer progression. The percentage of sarcopenia was 74.29%. Univariate Cox analysis identified that gender, PRAT, SAT, skeletal muscle (SM), sarcopenia, surgical technique, and tumor diameter were associated with progression. Further multivariate analysis showed that sarcopenia (hazard ratio [HR] 0.15, 95% confidence interval [CI] 0.03–0.66), SAT (HR 6.36, 95% CI 2.39–16.93), PRAT (HR 4.66, 95% CI 1.77–12.27), tumor diameter (HR 0.35, 95% CI 0.14–0.86), and surgical technique (HR 2.85, 95% CI 1.06–7.64) were independent risk factors for cancer progression. Then, a prognostic nomogram based on independent risk factors was constructed and the C-index for progression prediction was 0.831 (95% CI 0.761–0.901), representing a reasonable discrimination, the calibration curves, and the time-dependent ROC curves verified the good performance of the nomogram. Conclusions: A prognostic nomogram, including sarcopenia, SAT, PRAT, tumor diameter, and surgical technique, was constructed to calculate the probability of progression for localized pRCC patients and needs further external validation for clinical use in the future. [ABSTRACT FROM AUTHOR]

Purpose: To construct an effective prognostic nomogram for patients with clinically localized Acral lentiginous melanoma (ALM). Methods: This retrospective study included ALM patients from the Surveillance, Epidemiology, and End Results (SEER) database from 2004–2015. The 1686 cases were divided into the training and internal validation cohorts at a ratio of 7:3. The Cox regression analyses were performed to select risk factors for the nomogram. The performances of the nomogram were evaluated using the concordance index (C-index), area under receiver operating characteristic curve (AUC), and calibration plots, and validated in an external multicenter cohort. Results: Age, gender, race, and stage were significantly associated with overall survival (OS), with a C-index of 0.727 and 0.722 in the training and internal validation groups, respectively. The AUC of 2-,4-, and 6 years were higher than or equal to 0.75. Age, gender, race, site, and stage were related to ALM patients' CSS which have better C-index of 0.791 and 0.774 in the training and internal validation set. The AUC of 2-,4-, and 6- were higher than or equal to 0.80. Both survival calibration curves of 2-,4, and 6-year OS and CSS brought out a good consistency. The external multicenter cohort authenticated the value of the nomogram of OS, with a C-index of 0.657 and an AUC of 0.67, 0.72, and 0.65 at 2, 4, and 6 years. Good consistency was also observed. Conclusion: A prognostic nomogram was established and validated to help predict the survival of ALM patients and guide individualized treatment strategies. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study is to enhance the accuracy of monitoring and treatment information for patients diagnosed with colorectal cancer (CRC). Methods: Utilizing the Surveillance, Epidemiology, and End Results (SEER) database, a cohort of 335,948 eligible CRC patients was included in this investigation. Conditional survival probability and actuarial overall survival were employed as methodologies to investigate the association between clinicopathological characteristics and cancer prognosis. Results: Among CRC patients, the 5-year survival rate was 59%, while the 10-year survival rate was 42%. Over time, conditional survival showed a consistent increase, with rates reaching 45% and 48% for individuals surviving 1 and 2 years, respectively. Notably, patients with unfavorable tumor stages exhibited substantial improvements in conditional survival, thereby narrowing the disparity with actuarial overall survival over time. Conclusion: This study underscores the significance of time-dependent conditional survival probability, particularly for patients with a poorer prognosis. The findings suggest that long-term CRC survivors may experience improved cancer prognosis over time. [ABSTRACT FROM AUTHOR]

Background: Retroperitoneal liposarcoma (RPLS) is known for its propensity for local recurrence and short survival time. We aimed to identify a credible and specific prognostic biomarker for RPLS. Methods: Cases from The Cancer Genome Atlas (TCGA) sarcoma dataset were included as the training group. Co-expression modules were constructed using weighted gene co-expression network analysis (WGCNA) to explore associations between modules and survival. Survival analysis of hub genes was performed using the Kaplan–Meier method. In addition, independent external validation was performed on a cohort of 135 Chinese RPLS patients from the REtroperitoneal SArcoma Registry (RESAR) study (NCT03838718). Results: A total of 19 co-expression modules were constructed based on the expression levels of 26,497 RNAs in the TCGA cohort. Among these modules, the green module exhibited a positive correlation with overall survival (OS, p = 0.10) and disease-free survival (DFS, p = 0.06). Gene set enrichment analysis showed that the green module was associated with endocytosis and soft-tissue sarcomas. Survival analysis demonstrated that NINJ1, a hub gene within the green module, was positively associated with OS (p = 0.019) in the TCGA cohort. Moreover, in the validation cohort, patients with higher NINJ1 expression levels displayed a higher probability of survival for both OS (p = 0.023) and DFS (p = 0.012). Multivariable Cox analysis further confirmed the independent prognostic significance of NINJ1. Conclusions: We here provide a foundation for the establishment of a consensus prognostic biomarker for RPLS, which should not only facilitate medical treatment but also guide the development of novel targeted drugs. [ABSTRACT FROM AUTHOR]

Background: The tumor microbiome has been characterized in several malignancies; however, no previous studies have investigated its role in intrahepatic cholangiocarcinoma (ICC). Hence, we explored the tumor microbiome and its association with prognosis in ICC. Methods: One hundred and twenty-one ICC tumor samples and 89 adjacent normal tissues were profiled by 16S rRNA sequencing. Microbial differences between tumor and adjacent nontumoral liver tissues were assessed. Tumor microbial composition was then evaluated to detect its association with prognosis. Finally, a risk score calculated by the tumor microbiota was accessed by the least absolute shrinkage and selector operator method (Lasso) to predict prognosis of ICC. Results: The tumor microbiome displayed a greater diversity than that in adjacent nontumoral liver tissues. Tumor samples were characterized by a higher abundance of Firmicutes, Actinobacteria, Bacteroidetes, and Acidobacteriota. Higher tumor microbial α diversity was associated with lymph node metastasis and predicted shortened overall survival (OS) and recurrence-free survival (RFS). A total of 11 bacteria were selected to generate the risk score by Lasso. This score showed potential in predicting OS, and was an independent risk factor for OS. Conclusion: In conclusion, our study characterized the tumor microbiome and revealed its role in predicting prognosis in ICC. [ABSTRACT FROM AUTHOR]

Objective: To investigate the association between chronic headache outcome and aneurysmal wall enhancement (AWE) on high-resolution vessel wall imaging (HR-VWI) in patients with unruptured intracranial aneurysms (UIAs) who underwent microsurgical clipping. Methods: Two hundred seventy-four UIA patients were retrospectively analyzed. Patients were grouped according to presence of AWE. AWE was subclassified as focal or uniform. Clinical and imaging data were recorded. Headache was evaluated using the 10-point numerical rating scale and Headache Impact Test-6 before and 6 months after surgery. Results: The proportions of patients reporting chronic headache in the no AWE, focal wall enhancement (FWE), and uniform wall enhancement (UWE) groups were 5.7%, 24.8%, and 41.8%, respectively. All patients in the UWE group who reported headache before surgery experienced headache improvement after surgery. Decrease in headache severity was greater in the UWE group than in the FWE group. Multivariate binary logistic regression showed that FWE (odds ratio (OR) 0.490; 95% confidence interval (CI), 0.262–0.917; p = 0.026) and small intraluminal thrombus (OR 0.336; 95% CI, 0.142–0.795; p = 0.013) were independent factors protective against preoperative headache. FWE (OR 0.377; 95% CI, 0.195–0.728; p = 0.004) and small intraluminal thrombus (OR 0.235; 95% CI, 0.088–0.630; p = 0.004) were independent predictors of no headache relief after surgery. Conclusions: AWE on HR-VWI is associated with relief of chronic headache after surgical clipping in patients with UIAs. Incidence of chronic headache was highest in patients exhibiting UWE. These patients also experienced the greatest improvement in headache after surgical clipping. Clinical relevance statement: This study revealed that high-resolution vessel wall imaging can demonstrate aneurysmal wall plaque and intraluminal thrombus, which may be prognostic imaging markers for chronic headache in patients with unruptured intracranial aneurysms. Key Points: • Aneurysmal wall enhancement may be associated with chronic headache. • Incidence of chronic headache was highest in patients with aneurysms exhibiting uniform wall enhancement. • Patients with aneurysms exhibiting uniform wall enhancement experienced the greatest improvement in headache after clipping. [ABSTRACT FROM AUTHOR]

Background: The prevalence and mortality of bladder cancer (BLCA) present a significant medical challenge. While the function of senescence-related genes in tumor development is recognized, their prognostic significance in BLCA has not been thoroughly explored. Methods: BLCA transcriptome datasets were sourced from the TCGA and GEO repositories. Gene groupings were determined through differential gene expression and non-negative matrix factorization (NMF) methodologies. Key senescence-linked genes were isolated using singular and multivariate Cox regression analyses, combined with lasso regression. Validation was undertaken with GEO database information. Predictive models, or nomograms, were developed by merging risk metrics with clinical records, and their efficacy was gauged using ROC curve methodologies. The immune response's dependency on the risk metric was assessed through the immune phenomenon score (IPS). Additionally, we estimated IC50 metrics for potential chemotherapeutic agents. Results: Reviewing 406 neoplastic and 19 standard tissue specimens from the TCGA repository facilitated the bifurcation of subjects into two unique clusters (C1 and C2) according to senescence-related gene expression. After a stringent statistical evaluation, a set of ten pivotal genes was discerned and applied for risk stratification. Validity tests for the devised nomograms in forecasting 1, 3, and 5-year survival probabilities for BLCA patients were executed via ROC and calibration plots. IC50 estimations highlighted a heightened responsiveness in the low-risk category to agents like cisplatin, cyclopamine, and sorafenib. Conclusions: In summation, our research emphasizes the prospective utility of risk assessments rooted in senescence-related gene signatures for enhancing BLCA clinical oversight. [ABSTRACT FROM AUTHOR]

Background: Depression and anxiety are common mental disorders in patients with colorectal cancer (CRC); however, it remains unclear whether they are related to cancer mortality. Method: Based on a systematic literature search, 12 eligible studies involving 26,907 patients with CRC were included in this study. Results: Univariate analysis revealed that anxiety was associated with an all-cause mortality rate of 1.42 (1.02, 1.96), whereas multivariate analysis revealed that anxiety was not associated with an all-cause mortality rate of 0.73 (0.39, 1.36). In univariate and multivariate analyses, depression was associated with all-cause mortality rates of 1.89 (1.68, 2.13) and 1.62 (1.27, 2.06), respectively, but not with the cancer-associated mortality rate of 1.16 (0.91, 1.48) in multivariate analyses. Multivariate subgroup analysis of depression and all-cause mortality showed that younger age (≤65 years), being diagnosed with depression/anxiety after a confirmed cancer diagnosis, and shorter follow-up time (<5 years) were associated with poor prognosis. Conclusions: Our study emphasizes the key roles of depression and anxiety as independent factors for predicting the survival of patients with CRC. However, owing to the significant heterogeneity among the included studies, the results should be interpreted with caution. Early detection and effective treatment of depression and anxiety in patients with CRC have public health and clinical significance. [ABSTRACT FROM AUTHOR]

Background: Investigations elucidating the complex immunological mechanisms involved in colorectal cancer (CRC) and accurately predicting patient outcomes via bulk RNA-Seq analysis have been notably limited. This study aimed to identify the immune status of CRC patients, construct a prognostic model, and identify prognostic signatures via bulk RNA sequencing (RNA-seq) and single-cell RNA-seq (scRNA-seq). Methods: The scRNA-seq data of CRC were downloaded from Gene Expression Omnibus (GEO). The UCSC Xena database was used to obtain bulk RNA-seq data. Differentially expressed gene (DEG), functional enrichment, and random forest analyses were conducted in order to identify core genes associated with colorectal cancer (CRC) that were relevant to prognosis. A molecular immune prediction model was developed using logistic regression after screening features using the least absolute shrinkage and selection operator (LASSO). The differences in immune cell infiltration, mutation, chemotherapeutic drug sensitivity, cellular senescence, and communication between patients who were at high and low risk of CRC according to the predictive model were investigated. The prognostic genes that were closely associated with CRC were identified by random survival forest (RSF) analysis. The expression levels and clinical significance of the hub genes were analyzed in vitro. The LoVo cell line was employed to ascertain the biological role of thyroid hormone receptor-interacting protein 6 (TRIP6). Results: A total of seven main cell subtypes were identified by scRNA-seq analysis. A molecular immune predictive model was constructed based on the risk scores. The risk score was significantly associated with OS, stage, mutation burden, immune cell infiltration, response to immunotherapy, key pathways, and cell–cell communication. The functions of the six hub genes were determined and further utilized to establish a regulatory network. Our findings unequivocally confirmed that TRIP6 upregulation was verified in the CRC samples. After knocking down TRIP6, cell proliferation, migration, and invasion of LoVo cells were inhibited, and apoptosis was promoted. Conclusions: The molecular predictive model reliably distinguished the immune status of CRC patients. We further revealed that TRIP6 may act as an oncogene in CRC, making it a promising candidate for targeted therapy and as a prognostic marker for CRC. [ABSTRACT FROM AUTHOR]

Purpose: To elucidate the clinicopathological features and prognostic factors of minimal deviation adenocarcinoma (MDA) of the uterine cervix, a clinically rare but highly invasive disease. Methods: This was a retrospective, observational, real-world study of 43 patients with pathologically confirmed MDA at the Obstetrics and Gynaecology Hospital of Fudan University between November 2010 and November 2021. Baseline clinicopathological data were collected and reviewed. Prognostic factors for progression-free survival (PFS) and overall survival (OS) were investigated by univariate and multivariate Cox proportional hazards analyses. Results: Chief complaints included irregular vaginal discharge and/or bleeding (74.4%). Preoperative diagnosis was difficult, the detection rate was low (36.8%), all cases showed endophytic lesions, and 88.4% had deep stromal invasion, with biologically aggressive characteristics. The ovarian metastasis rate was high (16.3%, 7/43). The median maximum diameter of the tumour (MDOT) was 4.3 cm (range, 0.5–8.0 cm). MDOT was significantly associated with OS (P = 0.009), and the optimal cut-off value to define bulky MDA was 5.5 cm (P < 0.0001, χ= 21.161) using X-tile software. Independent prognostic factors included MDOT (HR = 10.095, P = 0.001) and ovarian metastasis (HR = 5.888, P = 0.008) for OS and MDOT (HR = 3.944, P = 0.028), ovarian metastasis (HR = 9.285, P = 0.001), and deep infiltration (HR = 3.627, P = 0.048) for PFS. Conclusion: Endophytic lesion development and ovarian metastasis are likely in MDA. A bulky tumour and ovarian metastasis indicate a worse prognosis. Given the special biological features of MDA, it is more appropriate to use 5.5 cm as the threshold for defining a bulky tumour than it is to use 4 cm. Ovary removal should be given higher priority to improve prognosis. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to develop and validate a novel prognostic nomogram to evaluate the survival benefit of hepatocellular carcinoma (HCC) patients receiving postoperative adjuvant transarterial chemoembolization (PA-TACE). Materials and methods: Clinical data of HCC patients who underwent hepatectomy at four medical centers were retrospectively analyzed, including those who received PA-TACE and those who did not. These two categories of patients were randomly allocated to the development and validation cohorts in a 7:3 ratio. Results: A total of 1505 HCC patients who underwent hepatectomy were included in this study, comprising 723 patients who did not receive PA-TACE and 782 patients who received PA-TACE. Among them, patients who received PA-TACE experienced more adverse events, although these events were mild and manageable (Grade 1–2, allp < 0.05). Nomograms were constructed and validated for patients with and without PA-TACE using independent predictors that influenced disease-free survival (DFS) and overall survival (OS). These two nomograms had C-indices greater than 0.800 in the development cohort and exhibited good calibration and discrimination ability compared to six conventional HCC staging systems. Patients in the intermediate-to-high-risk group in the nomogram who received PA-TACE had higher DFS and OS (all p < 0.05). In addition, tumor recurrence was significantly controlled in the intermediate-to-high-risk group of patients who received PA-TACE, while there was no significant difference in the low-risk group of patients who received PA-TACE. Conclusion: The nomograms were developed and validated based on large-scale clinical data and can serve as online decision-making tools to predict survival benefits from PA-TACE in different subgroups of patients. [ABSTRACT FROM AUTHOR]

This study aimed to examine the characteristics and treatment outcomes of patients with TP53-mutant acute myeloid leukaemia (AML) and to explore potential prognostic factors. This retrospective analysis included 130 patients diagnosed with TP53-mutant AML at the Fujian Medical University Union Hospital between January 2016 and June 2023. Patients' ages ranged from 17 to 80 years, with a median age of 59 years. The proportions of de novo, therapy-related, and secondary AML cases were 71.5%, 7.7%, and 20.8%, respectively. Complex karyotypes were observed in 60.6% of patients, and the proportions of -5 or del(5q), -7 or del(7q), and − 17 or del(17p) were 41.7%, 27.9% and 14.4%, respectively. DNA methylation- and myelodysplasia-related (MR) gene mutations were observed in 36.9% and 25.4% of patients, respectively. These patients showed poor survival, with a median overall survival (OS) of 4.5 months, a 1-year OS rate of 32.5%, a 3-year OS rate of 18.8%, and a 5-year OS rate of 11.3%. The complete response rates for intensive chemotherapy (IC), hypomethylating agent (HMAs)-based therapies, and azacitidine plus venetoclax were 35.7%, 22.2%, and 37.5%, respectively. Patients who did or did not receive allogeneic haematopoietic stem cell transplantation (allo-HSCT) had similar prognoses (median OS: 6.0 vs. 3.9 months; P = 0.6415). Multivariate analysis indicated that MR gene mutations is an independent favorable prognostic factor of OS (HR = 0.366, 95% CI: 0.181–0.738, P = 0.005). In conclusion, patients with TP53-mutant AML have poor prognoses under current treatment strategies and MR gene mutations are associated with a more favorable survival. Therefore, further studies are needed to improve the survival rates in this population. [ABSTRACT FROM AUTHOR]

Background: Symptoms of cauda equina syndrome (CES) secondary to degenerative lumbar spine diseases are sometimes mild and tend to be ignored by patients, resulting in delayed treatment. In addition, the long-term efficacy of surgery is unclear. Objective: To determine the predictive factors of CES and post-operative recovery in patients with symptoms lasting > 3 months. Methods: From January 2011 to December 2020, data of 45 patients with CES secondary to lumbar disk herniation/lumbar spinal stenosis were collected from a single center. The patients had bladder, bowel or sexual dysfunction and decreased perineal sensation that lasted for > 3 months. A 2-year post-operative follow-up was conducted to evaluate recovery outcomes, which were measured by validated self-assessment questionnaires conducted by telephone and online. Results: Overall, 45 CES patients (57.8% female; mean age, 56 years) were included. The duration of pre-operative CES symptoms was 79.6 weeks (range, 13–730 weeks). The incidence of saddle anesthesia before decompression was 71.1% (n = 32), bladder dysfunction 84.4% (n = 38), bowel dysfunction 62.2% (n = 28) and sexual dysfunction 64.4% (n = 29). The overall recovery rate of CES after a 2-year follow-up was 64.4%. The rates of the residual symptoms at the last follow-up were as follows: saddle anesthesia 22.2%, bladder dysfunction 33.3%, bowel dysfunction 24.4% and sexual dysfunction 48.9%. Pre-operative saddle anesthesia, overactive bladder and sexual dysfunction were risk factors for poor prognosis after decompression. Conclusion: CES patients with symptoms lasting > 3 months may recover after surgery. Sexual dysfunction has a high residual rate and should not be ignored during diagnosis and treatment. [ABSTRACT FROM AUTHOR]

Methyltransferase-like protein 7A (METTL7A) is an m6A RNA methyltransferase that has been linked to cancer prognosis and drug resistance. However, a comprehensive analysis of METTL7A is lacking. The expression of METTL7A, prognostic performance, correlation with microsatellite instability (MSI), tumor mutational burden (TMB), and immune infiltration was investigated in The Cancer Genome Atlas (TCGA). Immunohistochemistry staining was applied to detect METTL7A in 6 tumors. METTL7A was significantly decreased in 19 cancers in TCGA including LUAD. Alterations of METTL7A include amplification and mutation, and epigenetic alterations revealed increased promoter methylation may result in down-regulation of METTL7A in LUAD. We also found that METTL7A was linked to both TMB and MSI in LUAD. METTL7A was increasingly correlated with invasive immune cells, while being negatively associated with Macrophages M0, Mast cells activated, activated memory CD4 T cells, CD8 T cells, and follicular helper T cells in several tumors. Additionally, METTL7A showed similar correlation with immune therapy-related genes across cancers. Our biological validation found that the protein levels of METTL7A were down-regulated in breast cancer (BRCA), endometrioid cancer (UCEC), colon cancer (COAD), prostate cancer (PRAD), and kidney clear cell carcinoma (KIRC), as detected by immunohistochemistry staining. Overall, our work indicates that METTL7A may serve as promising diagnostic and prognostic indicator of LUAD, and our work sheds light on the potential immunological and prognostic roles of METTL7A in human cancers. [ABSTRACT FROM AUTHOR]

Background: Numerous studies have highlighted the crucial value of the heavy chain of ferritin (FTH1) as a key regulator of iron metabolism and a suppressor of ferroptosis, intimately tied to the tumor immune microenvironment (TIME). Nevertheless, the precise impact of FTH1 on cancer immunotherapy remains vague. Our study aims to systematically explore the prognostic significance and immune role of FTH1 in pan-cancers immunotherapy. Methods: Our study delves into the potential of FTH1 as an immunotherapeutic target within the TIME of various solid cancers. The immune landscape and underlying mechanisms of FTH1 in the TIME were investigated by multiple algorithms and bioinformatics methods. Single-cell sequencing analysis and multiplex immunofluorescence staining techniques are applied to observe FTH1 co-expression on both tumor and immune cells. Results: FTH1 exhibited aberrant expression patterns across multiple cancers, which is strongly correlated with immunotherapy resistance. Patients with high FTH1 expression levels tended to derive less benefit from immunotherapies. Moreover, FTH1 demonstrated a significant correlation with TIME infiltration, immune checkpoint molecules, and immune-related pathways. Notably, FTH1 showed a positive association with macrophage infiltrations, its expression was particularly noteworthy in malignant cells and macrophages. Inhibiting FTH1-related signaling pathways appeared to be a potential strategy to counteract tumor immunotherapy resistance. Conclusion: Our comprehensive analyses may offer valuable insights into the role of FTH1 in tumor immunotherapy. The observed correlations pave the way for further functional experiments, fostering an enhanced understanding that could shape future research endeavors. [ABSTRACT FROM AUTHOR]

PIK3CA mutations have important therapeutic and prognostic implications in various cancer types. However, highly sensitive detection of PIK3CA hotspot mutations in heterogeneous tumor samples remains a challenge in clinical settings. To establish a rapid PCR assay for highly sensitive detection of multiple PIK3CA hotspot mutations. We described a novel melting curve analysis-based assay using looping-out probes that can enrich target mutations in the background of excess wild-type and concurrently reveal the presence of mutations. The analytical and clinical performance of the assay were evaluated. The developed assay could detect 10 PIK3CA hotspot mutations at a mutant allele fraction of 0.05–0.5% within 2 h in a single step. Analysis of 82 breast cancer tissue samples revealed 43 samples with PIK3CA mutations, 28 of which were confirmed by Sanger sequencing. Further testing of 175 colorectal cancer tissue samples showed that 24 samples contained PIK3CA mutations and 19 samples were confirmed by Sanger sequencing. Droplet digital PCR supported that all mutation-containing samples undetected by sequencing contained mutations with a low allele fraction. The rapidity, ease of use, high sensitivity and accuracy make the new assay a potential screening tool for PIK3CA mutations in clinical laboratories. [ABSTRACT FROM AUTHOR]

Cuprotosis, an emerging mode of cell death, has recently caught the attention of researchers worldwide. However, its impact on low-grade glioma (LGG) patients has not been fully explored. To gain a deeper insight into the relationship between cuprotosis and LGG patients' prognosis, we conducted this study in which LGG patients were divided into two clusters based on the expression of 18 cuprotosis-related genes. We found that LGG patients in cluster A had better prognosis than those in cluster B. The two clusters also differed in terms of immune cell infiltration and biological functions. Moreover, we identified differentially expressed genes (DEGs) between the two clusters and developed a cuprotosis-related prognostic signature through the least absolute shrinkage and selection operator (LASSO) analysis in the TCGA training cohort. This signature divided LGG patients into high- and low-risk groups, with the high-risk group having significantly shorter overall survival (OS) time than the low-risk group. Its predictive reliability for prognosis in LGG patients was confirmed by the TCGA internal validation cohort, CGGA325 cohort and CGGA693 cohort. Additionally, a nomogram was used to predict the 1-, 3-, and 5-year OS rates of each patient. The analysis of immune checkpoints and tumor mutation burden (TMB) has revealed that individuals belonging to high-risk groups have a greater chance of benefiting from immunotherapy. Functional experiments confirmed that interfering with the signature gene TNFRSF11B inhibited LGG cell proliferation and migration. Overall, this study shed light on the importance of cuprotosis in LGG patient prognosis. The cuprotosis-related prognostic signature is a reliable predictor for patient outcomes and immunotherapeutic response and can help to develop new therapies for LGG. [ABSTRACT FROM AUTHOR]

Anti-neutrophil cytoplasmic antibody (ANCA)–associated vasculitis (AAV) patients with dual positivity for proteinase 3-ANCA (PR3-ANCA) and myeloperoxidase-ANCA (MPO-ANCA) are uncommon. We aimed to investigate these idiopathic double-positive AAV patients’ clinical features, histological characteristics, and prognosis. We reviewed all the electronic medical records of patients diagnosed with AAV to obtain clinical data and renal histological information from January 2010 to December 2020 in a large center in China. Patients were assigned to the MPO-AAV group or PR3-AAV group or idiopathic double-positive AAV group by ANCA specificity. We explored features of idiopathic double-positive AAV. Of the 340 patients who fulfilled the study inclusion criteria, 159 (46.76%) were female, with a mean age of 58.41 years at the time of AAV diagnosis. Similar to MPO-AAV, idiopathic double-positive AAV patients were older and had more severe anemia, lower Birmingham Vasculitis Activity Score (BVAS) and C-reactive protein (CRP) levels, less ear, nose, and throat (ENT) involvement, higher initial serum creatinine and a lower estimated glomerular filtration rate (eGFR) when compared with PR3-AAV (P < 0.05). The proportion of normal glomeruli of idiopathic double-positive AAV was the lowest among the three groups (P < 0.05). The idiopathic double-positive AAV patients had the worst remission rate (58.8%) among the three groups (P < 0.05). The relapse rate of double-positive AAV (40.0%) was comparable with PR3-AAV (44.8%) (P > 0.05). Although there was a trend toward a higher relapse rate of idiopathic double-positive AAV (40.0%) compared with MPO-AAV (23.5%), this did not reach statistical significance (P > 0.05). The proportion of patients who progressed to ESRD was 47.1% and 44.4% in the idiopathic double-positive AAV group and MPO-AAV group respectively, without statistical significance. Long-term patient survival also varied among the three groups (P < 0.05). Idiopathic double-positive AAV is a rare clinical entity with hybrid features of MPO-AAV and PR3-AAV. MPO-AAV is the “dominant” phenotype in idiopathic double-positive AAV. [ABSTRACT FROM AUTHOR]

Despite numerous reports indicating the significant impact of RNA modification on malignant glioblastoma (GBM) cell behaviors such as proliferation, invasion and therapy efficacy, its specific involvement in glioblastoma (GBM) angiogenesis is remains unclear and is currently under investigation. In this study, we aimed to investigate the relevance between RNA modification regulators and GBM angiogenesis. Our study employed bioinformatic analyses, including Gene Set Enrichment Analysis (GSEA), differential expression analysis, and Kaplan–Meier survival analysis, to identify regulators of angiogenesis-associated RNA modification (RM). Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to identify the enrichment of angiogenesis associated signatures in ALKBH5-high expression GBMs. We also utilized Western blot to verify the upregulation of ALKBH5 in clinical GBM samples. By a series of in vitro and in vivo assays, including plasmid transfection, wound healing, transwell invasion test, tube formation, RT-qPCR, ELISA assays and xenograft mice model, we validated the angiogenesis regulation ability of ALKBH5 in GBM. The N6-methyladenosine (m6A) modification "erase" ALKBH5 emerged as a candidate regulator associated with angiogenesis, demonstrating elevated expression and robust prognostic predictive ability in GBM patients. We also revealed enrichment of vasculature development biological process in GBMs with high ALKBH5 expression. Subsequently, we validated the elevated the expression of ALKBH5 in clinical GBM and paired adjacent tissues through western blot. Additionally, we knocked down the expression of ALKBH5 using sh-RNAs in U87 GBM cells to access the angiogenesis induction ability in U87 cells. In vitro experiments, Human Umbilical Vein Endothelial Cells (HUVECs) were used to perform wound healing, transwell migration and tube formation analysis, results indicated that ALKBH5 knock-down of U87 cells could decrease the pro-angiogenesis ability of U87 GBM cells. Further validation of our bioinformatic findings confirmed that ALKBH5 knockdown impaired VEGFA secretion in both in vitro and in vivo settings in U87 cells. These results comprehensively affirm the crucial role of ALKBH5 in regulating GBM-induced angiogenesis, both in vitro and in vivo. ALKBH5 not only emerges as a promising prognostic factor for GBM patients, but also plays a pivotal role in sustaining GBM progression by promoting angiogenesis. [ABSTRACT FROM AUTHOR]

Background: Mesothelin (MSLN) has been implicated in cancer migration, invasion, and prognosis, making it a potential tumor marker. However, the precise role of MSLN in the migration and invasion of malignant pleural mesothelioma (MPM) remains elusive, and effective noninvasive methods for assessing MSLN status are currently lacking. In this study, we focused on MSLN expression and elucidated the underlying mechanisms by which MSLN regulates migration and invasion in MPM. Building upon this knowledge, we developed an MRI nanoprobe that targets MSLN to assess its status in vitro and in vivo by comparing T2 signal intensity and T2 values on magnetic resonance imaging examinations. This nanoprobe combines the anatomical information obtained from MRI with biological information obtained from MSLN for comprehensive evaluation of MPM. Results: Notably, we observed that MSLN expression in the epithelial type of MPM was higher and increased continuously with tumor growth than that in other types. In addition, MSLN upregulation promoted N-cadherin, matrix metalloproteinase-7, and MMP9 expression and resulted in higher migration/invasion ability and shorter survival. We synthesized MSLN-targeted nanoprobes (Fe3O4@SiO2-PEG-MSLN, FSPM) to assess MSLN expression by comparing the T2 signal intensity and T2 value of different cell lines and mice after 14, 28, and 42 days of modeling. Remarkably, MSLN-targeted nanoprobes demonstrated excellent targeting capabilities. In vitro studies revealed a pronounced reduction in T2 signal intensity and T2 values of the epithelial type as the probe concentration increased. In addition, in vivo experiments demonstrated a gradual decline in these parameters over time, particularly in the epithelial type as compared to the biphasic type, corresponding to the dynamic expression patterns of MSLN during different growth stages. Conclusion: Our comprehensive research succeeded in confirming the regulatory mechanisms by which MSLN influences migration and invasion. Moreover, we introduced a promising method for monitoring MSLN expression that may help in facilitating the early detection, histological subtype identification, and assessment of migration, invasion, and prognosis in MPM. [ABSTRACT FROM AUTHOR]

Background: The worldwide incidence of acute pancreatitis (AP) is increasing, but the dominant etiology of AP may vary by country. Mixed etiologies are involved in the increase in the number of AP patients. Aims: This study was to analyze the etiological changes and prognosis of AP patients and explore the prognosis of AP patients with mixed etiologies. Methods: Using a retrospective analysis method, AP patients hospitalized from January 2007 to December 2021 were selected from a pancreatic center in Nanchang, China. Trends in the main etiologies were analyzed, and the severity and prognosis of different etiologies were compared. Results: A total of 10,071 patients were included. Cholelithiasis (56.0%), hyperlipidemia (25.3%), and alcohol (6.5%) were the top three etiologies. The proportion of acute biliary pancreatitis (ABP) showed a decreasing trend, while the proportion of hypertriglyceridemic pancreatitis (HTGP) and alcoholic AP showed an increasing trend (all ptrend < 0.001). The incidence of organ failure and necrotizing pancreatitis was higher in patients with HTGP than in those with AP induced by other etiologies (all p < 0.05). There was no statistically significant difference in mortality among patients with different etiologies. Patients with AP due to a mixed hypertriglyceridemia-alcoholic etiology had higher ICU admission rates and were more severe than those with AP induced by other mixed etiologies. Conclusion: In the past 15 years, the proportion of ABP has trended downward, while those of HTGP and alcoholic AP have risen. Among patients with mixed etiologies, those with a mixed hypertriglyceridemia-alcoholic etiology had a worse prognosis. [ABSTRACT FROM AUTHOR]

Mitochondrial metabolism has been shown to play a key role in immune cell survival and function, but mitochondrial creatine kinase 2 (CKMT2) has been relatively little studied about tumor immunity. We aimed to explore the prognostic value of CKMT2 in 33 cancer types and investigate its potential immune function. We used a range of bioinformatics approaches to explore the potential carcinogenic role of CKMT2 in multiple cancers. CKMT2 was lowly expressed in 14 tumor tissues and highly expressed in 4 tumor tissues. Immunohistochemical assays showed overexpression of CKMT2 in colon cancer and rectal cancer. CKMT2 overexpression was positively correlated with the prognosis of lung adenocarcinoma and prostate cancer. CKMT2 overexpression is mainly enriched in the adaptive immune system and immune regulatory pathways of immunoglobulins. Seven cancers were positively correlated with low CKMT2 expression in tumor microenvironment analysis. Among the five cancers, low expression of CKMT2 resulted in better immunotherapy treatment outcomes. There was a strong correlation between CKMT2 and most immune-related genes in specific cancer types. CKMT2 plays an important role in tumorigenesis and cancer immunity and can be used as a prognostic biomarker and potential target for cancer immunotherapy. [ABSTRACT FROM AUTHOR]

Despite the remarkable efficacy of PD-1-associated immune checkpoint inhibitors in treating cutaneous melanoma (CM), the inconsistency in the expression of PD-1 and its ligand PD-L1, and resulting variability in the effectiveness of immunotherapy, present significant challenges for clinical application. Therefore, further research is necessary to identify tumor-related biomarkers that can predict the prognosis of immunotherapy. Tertiary lymphoid structures (TLSs) have been recognized as a crucial factor in predicting the response of immune checkpoint inhibitors in solid tumors, including CM. However, the study of TLSs in CM is not yet comprehensive. Gene expression profiles have been shown to correlate with CM risk stratification and patient outcomes. In this study, we identified TLS-related genes that can be used for prognostic purposes and developed a corresponding risk model. The impact of TLS-related genes on clinicopathological characteristics, immune infiltration and drug susceptibility was also explored. Our biological function enrichment analysis provided preliminary evidence of related signaling pathways. Our findings provide a new perspective on risk stratification and individualized precision therapy for CM. [ABSTRACT FROM AUTHOR]

Purpose: Peritoneal metastasis in gastric cancer (GC) is a late-stage condition with a poor prognosis. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is a popular treatment for peritoneal metastases. Here, we aim to investigate the real-world application and efficacy of HIPEC alone for GC patients with synchronous peritoneal metastases. Methods: We conducted a retrospective analysis on GC patients with synchronous peritoneal metastasis at the Sixth Affiliated Hospital of Sun Yat-sen University between January 2011 and December 2022. Survival analyses and Cox regression models were performed based on overall survival (OS) and cancer-specific survival (CSS), and subgroup analysis was used to determine the prognostic value of HIPEC across different treatment. Results: We enrolled 250 patients, of whom 120 (48%) received HIPEC while 130 (52%) did not. HIPEC showed no survival benefit for GC patients (P = 0.220 for OS and P = 0.370 for CSS). However, subgroup analysis found that HIPEC can only improve OS and CSS when combined with primary tumor resection (P = 0.034 for OS and P = 0.036 for CSS). Moreover, survival analyses also demonstrated that HIPEC independently improved OS (HR for OS = 0.58, 95% CI 0.37–0.92, P = 0.020) and CSS (HR for CSS = 0.58, 95% CI 0.37–0.93, P = 0.024) for patients who underwent primary site resection, but not for those who did not. Conclusion: HIPEC can improve survival in GC patients with synchronous peritoneal metastases who have primary tumor resection, but not in those without primary tumor resection. [ABSTRACT FROM AUTHOR]

Worldwide, primary liver cancer is the third leading cause of cancer-related death. Hepatocellular carcinoma (HCC) accounts for the majority of primary liver cancers. Recent studies have shown that circular RNAs (circRNAs) that interact with microRNAs (miRNAs) are involved in the occurrence and development of various tumours. Transcriptional profile analysis was used to analyse expression of circRNAs in HCC in this study. The top ten upregulated circRNAs were selected and validated by quantitative reverse transcription polymerase chain reaction (qRT-PCR) in another 34 HCC patients. MiRNAs and mRNAs downstream of these circRNAs were explored through database analysis, and finally, the competitive endogenous RNA (ceRNA) networks were constructed for 5 selected circRNAs. We identified 9658 differentially expressed circRNAs by transcriptional profile analysis. QRT-PCR was performed to validate the top ten upregulated circRNAs, and five circRNAs were selected for further analysis. The miRNAs and mRNAs downstream of these five circRNAs were predicted to construct ceRNA network diagrams. Further analysis revealed five circRNA–miRNA–mRNA axes that correlate negatively with HCC prognosis. Numerous differentially expressed circRNAs exist in HCC, and they can regulate the biological behaviour of HCC through ceRNA networks. Bioinformatics analysis showed that ceRNA regulatory axes involved in HCC have high diagnostic and prognostic value and deserve further exploration. [ABSTRACT FROM AUTHOR]

Objective: To establish a nomogram for prediction of prognosis in EGFR-positive advanced nasopharyngeal carcinoma (NPC) patients who were treated with induction chemotherapy (IC) and concurrent chemoradiotherapy (CCRT). The clinical data of 124 NPC patients who received IC sequential CCRT combined with targeted therapy at the Department of Oncology of the Affiliated Hospital of North Sichuan Medical College between June 2017 and September 2022 were retrospectively reviewed. Logistic regression analysis was used to identify the prognostic factors for building the nomogram. Results: Multifactorial regression analysis showed that the use of targeted drugs and T stage were independent factors of prognosis (p < 0.05) and the equation Y = 0.476 + 2.733X1 + − 0.758 × 2 (Y = efficacy, X1 = targeted drug therapy, X2 = T stage) was obtained. Then, a prognostic nomogram prediction model was constructed. The prediction model was validated internally for 1000 times using the Bootstrap resampling method with an accuracy of 79.29%. The calibration curve suggests that the predicted values fit well with the true values. The clinical decision curve (DCA) shows that the model has good clinical predictive value. Conclusion: The use of targeted therapy significantly improved the prognosis of patients with EGFR-positive advanced NPC. For advanced NPC patients with T1 and T2 stages, IC sequenced with CCRT is more effective, and the addition of targeted therapy can further improve patients' prognosis. For advanced NPC patients with T3 and T4 stages, IC sequenced with CCRT is ineffective, and the addition of targeted therapy can significantly improve patient prognosis. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the effects of cancer-associated fibroblasts (CAFs)-related genes on prognosis and immunity in ovarian cancer. The gene expression profile data and clinical data of ovarian cancer were obtained from TCGA and GEO databases. The differentially expressed genes (DEGs) between tumor and normal tissues were selected, and the infiltration of immune cells, stromal cells and CAFs in each sample was evaluated. WGCNA was used for CAFs signature genes identification. CAFs score was calculated, followed by comparison of prognosis, immune cells, pathway and drug susceptibility between CAFs score-high and -low groups. There were significant differences in immune and stromal score as well as CAFs ratio between two groups. A total of 6474 DEGs were identified. By WGCNA, six CAFs signature genes, including MMP1, DPYSL4, PDGFRA, OGN, FBXL7 and NUDT10, were identified. CAFs score was an independent prognostic factor. There was a significant correlation between the actual prognosis and the different CAFs score groups. The proportion of five immune cells was significantly different between two CAFs score groups. Nine signaling pathways, such as epithelial-mesenchymal transition and angiogenesis, were different between two groups. Five chemotherapeutic drugs, such as paclitaxel and gefitinib, were found to be significantly different in IC50 levels between two groups. The six CAFs signature genes, including MMP1, DPYSL4, PDGFRA, OGN, FBXL7 and NUDT10, may serve as prognostic biomarkers and therapeutic targets of ovarian cancer. [ABSTRACT FROM AUTHOR]

Purpose: To establish and validate a multiparameter prediction model for early recurrence after radical resection in patients diagnosed with combined hepatocellular-cholangiocarcinoma (cHCC-CC). Materials and methods: This study reviewed the clinical characteristics and preoperative CT images of 143 cHCC-CC patients who underwent radical resection from three institutions. A total of 110 patients from institution 1 were randomly divided into training set (n = 78) and testing set (n = 32) in the ratio of 7–3. Univariate and multivariate logistic regression analysis were used to construct a nomogram prediction model in the training set, which was internally and externally validated in the testing set and the validation set (n = 33) from institutions 2 and 3. The area under the curve (AUC) of receiver operating characteristics (ROC), decision curve analysis (DCA), and calibration analysis were used to evaluate the model's performance. Results: The combined model demonstrated superior predictive performance compared to the clinical model, the CT model, the pathological model and the clinic-CT model in predicting the early postoperative recurrence. The nomogram based on the combined model included AST, ALP, tumor size, tumor margin, arterial phase peritumoral enhancement, and MVI (Microvascular invasion). The model had AUCs of 0.89 (95% CI 0.81–0.96), 0.85 (95% CI 0.70–0.99), and 0.86 (95% CI 0.72–1.00) in the training, testing, and validation sets, respectively, indicating high predictive power. DCA showed that the combined model had good clinical value and correction effect. Conclusion: A nomogram incorporating clinical characteristics and preoperative CT features can be utilized to effectively predict the early postoperative recurrence in patients with cHCC-CC. [ABSTRACT FROM AUTHOR]