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Objective: To analyze the changes in tumor necrosis factor receptor superfamily (TNFRSF) 4 expression levels in laryngeal squamous cell carcinoma (LSCC) patients through multiple database data combined with clinical samples, and to study the role of TNFRSF4 in the occurrence and development of LSCC. Method: Based on Gene Expession Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database, the differentially expressed gene was screened out. The expression level prediction and survival analysis of TNFRSF4 were performed using Gene Expression Profiling Interactive Analysis (GEPIA) database. Western blot and qRT-PCR were performed on LSCC and adjacent tissue samples from three patients. K-M curve was drawn based on TCGA clinical data, and Cox regression analysis was performed. Finally, gene set enrichment analysis was performed to explore signaling pathways related to the role of TNFRSF4 in LSCC. Results: In the database and clinical samples, the expression of TNFRSF4 in the LSCC group was higher than that in the normal group (P＜0.05), and the survival rate of the high TNFRSF4 expression group was higher than that of the low TNFRSF4 expression group (P＜0.01). Multivariate Cox regression analysis showed that the expression level of TNFRSF4 (HR: 0.430, 95%CI: 0.229-0.806, P=0.009), gender (HR: 0.424, 95%CI: 0.204-0.882, P=0.022), lymph node staging (HR:2.010, 95%CI: 1.055-3.831, P=0.034) and distant metastasis (HR: 3.706, 95%CI: 1.152-11.922, P=0.028) collectively affect the overall survival time of patients. The results of gene set enrichment analysis showed that the most significantly correlated signaling pathways with TNFRSF4 expression included cell adhesion molecule, JAK-STAT signaling pathway, T cell receptor signaling pathway, B cell receptor signaling pathway, primary immunodeficiency, and autoimmune thyroid disease. Conclusion: High expression of TNFRSF4 may be a biomarker for good prognosis of patients with LSCC.

Previous reports indicate that Cdc42-interacting protein-4 (CIP4) has previously been reported to plays an important role in the progression of various cancers. However, its correlation with laryngeal cancer (LC) remains unreported. Data from TCGA and GEO databases were used to evaluate the role of CIP4 in LC. Based on GEO and TCGA datasets, we analyzed the differences in CIP4 expression between normal and tumor samples. The Wilcoxon signed-rank test was used to analyze the relationship between clinical features and CIP4. Cox regression and the Kaplan-Meier analyses were used to identify the clinical characteristics associated with the overall survival. Also, the GEPIA database was used to confirm the relationship between CIP4 and overall survival. Lastly, Gene Set Enrichment Analysis (GSEA) was performed based on the TCGA dataset. CIP4 expression in LC was significantly associated with gender and tumor stage (p-values<0.05). Similar to GEPIA validation, Kaplan-Meier survival analysis demonstrated that LC with CIP4-low exhibited a worse prognosis than that with CIP4-high. Univariate analysis revealed that CIP4-high significantly correlated with better overall survival (HR: 0.522, 95% CI: 0.293–0.830, P = 0.026). Besides, multivariate analysis revealed that CIP4 remained independently associated with the overall survival (HR: 0.61, 95% CI: 0.326–0.912, P = 0.012). GSEA showed that the p53, WNT signaling, TGF-β signaling pathways, etc. were enriched in a phenotype high CIP4 expression. In summary, the CIP4 gene is a potential prognostic molecular marker for patients diagnosed with laryngeal cancer. Moreover, the p53, WNT signaling, and TGF-β signaling pathways are potentially associated with CIP4 in LC. [ABSTRACT FROM AUTHOR]

Background: Patients with a prior history of cancer are commonly excluded from clinical trial. Increasing number of studies implied that a prior cancer did not adversely affect the clinical outcome among various types of cancer patients. However, the impact of prior cancer on survival of larynx cancer patients remains largely unknown. The aim of this study was to evaluate the prevalence of prior cancer and assess its impact on survival of patients diagnosed with larynx cancer.Methods: Patients with larynx cancer as the first or second primary malignancy diagnosed from 2004 to 2015 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Propensity score matching (PSM) was conducted to balance baseline characteristics. Kaplan-Meier method, multivariate Cox proportional hazard model, and multivariate competing risk model were performed for survival analysis.Results: A total of 24,812 eligible patients with larynx cancer were included in the study, wherein a total of 2436 patients (9.8%) had a prior history of cancer. Prostate (36%), lung and bronchus (10%), urinary bladder (7%), and breast (6%) were the most common types of prior cancer. A prior cancer history served as a risk factor for overall survival (AHR =1.30; 95% CI [1.21-1.41]; P < 0.001) but a protective factor for cancer-specific mortality (AHR = 0.83; 95% CI [0.72-0.94]; P = 0.004) in comparison with those without prior cancer. The subgroup analysis showed that a prior history of cancer adversely affected overall survival of patients with larynx cancer in most subgroups stratified by timing and types of prior cancer, as well as by different clinicopathologic features.Conclusion: Our study indicated an adverse survival impact of a prior history of cancer on patients with larynx cancer. Except for a few particular prior cancer, clinical trials should be considered prudently for laryngeal cancer patients with prior cancers. [ABSTRACT FROM AUTHOR]