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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.

Interleukin-6 (IL-6) is one of the most important cytokines which has been shown to play a critical role in the pathogenesis of cholesteatoma. In this study, we aimed to investigate the expression of interleukin-6 (IL-6) and phosphorylated signal transducer and activator of transcription 3 (p-STAT3) in middle ear cholesteatoma epithelium in an effort to determine the role of IL-6/JAK/STAT3 signaling pathway in the pathogenesis of cholesteatoma. Immunohistochemistry was used to examine the expression of IL-6 and p-STAT3 in 25 human middle ear cholesteatoma samples and 15 normal external auditory canal (EAC) epithelium specimens. We also analyzed the relation of IL-6 and p-STAT3 expression levels to the degree of bone destruction in cholesteatoma. We found that the expression of IL-6 and p-STAT3 were significantly higher in cholesteatoma epithelium than in normal EAC epithelium (p<0.05). In cholesteatoma epithelium, a significant positive association was observed between IL-6 and p-STAT3 expression (p<0.05). However, no significant relationships were observed between the degree of bone destruction and the levels of IL-6 and p-STAT3 expression (p>0.05). To conclude, our results support the concept that IL-6/JAK/STAT3 signaling pathway is active and may play an important role in the mechanisms of epithelial hyper-proliferation responsible for cholesteatoma.