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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.

Tissue-resident macrophages (TRMØs) can act as innate-immune sentinels to protect body against microbe invaders and stimulating materials such as cholesterol crystals in cholesteatoma, as well as to preserve tissue integrity by cleaning unwanted cellular debris. TRMØs in the incised middle ear tissues were obtained from the patients with cholesteatoma as an experimental group and the patients without cholesteatoma as a control group. Differential gene expression profiling of TRMØs was conducted between two groups by analyzing GO processes, KEGG and GSEA pathways of inflammation, tissue repair and homeostasis. The current study showed that 145 of 7060 genes were significantly up-regulated (logFC>2 and FDR <0.05) when compared with the patients without cholesteatoma. GO process, GSEA and Cytoscape analysis of the over-expressed genes illustrated the boosted inflammatory and anti-infection functions of TRMØs existed neutrophil function, leukocyte migration, and adaptive immune response involved receptors and signaling pathways. Whereas the homeostasis and repair functions of TRMØs were affected from up-regulated genes, such as over-expressed keratin-13 that helped form the outer keratinising squamous epithelial layer, and over-expressed MMPs that activated the extracellular matrix molecules to promote inflammation and disturb tissue remodeling. Additionally, 74 down-regulated genes (logFC<-2 and FDR <0.05) also affected the homeostasis and repair functions by affecting extracelluar matrix structure and contractile fibres in TRMØs. The cellular and molecular levels in cholesteatoma is attributable to chronic infection and several disturbed cellular biological processes involving cell integrity and tissue remodeling. [ABSTRACT FROM AUTHOR]