TNFRSF10B, a Therapeutic Target for Oral Squamous Cell Carcinoma Through Integrated Bioinformatics and Preliminary Experiments.

BackgroundTumor necrosis factor receptor superfamily member (10B TNFRSF10B), as a key apoptosis regulator of Oral Squamous Cell Carcinoma (OSCC), exerts a critical effect on its development.MethodsDifferentially expressed genes in OSCC (GSE25099) were screened first. Weighted gene co-expression network analysis identified gene modules, followed by Lasso regression and Cox modeling to pinpoint pivotal genes. Expression was validated in the Cancer Genome Atlas databases and in clinical samples. The Search Tool for the Retrieval of Interacting Genes/Proteins database was used to generate a protein-protein interaction (PPI) network, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses explored biological functions. Then, for in vitro assays, core gene-targeted siRNAs were introduced into SCC-4 and SCC-9 cell lines to mediate gene knockdown. Cell proliferation was quantified by the CCK-8 method, and apoptotic activity was assessed via flow cytometry, TUNEL staining, and Western blotting for apoptosis-associated proteins.ResultsAmong the 10 core genes that were further screened, TNFRSF10B was most notably linked to unfavorable OSCC prognosis and showed strong diagnostic power. Additionally, its overexpression was associated with clinical stage, nodal metastasis, and chemoresistance. PPI and enrichment analyses revealed its role in extrinsic and necroptotic apoptosis. Moreover, the knockdown of TNFRSF10B suppressed viability and induced apoptosis by upregulating Bax, downregulating Bcl-2, and activating Caspase-3/PARP.ConclusionsTNFRSF10B drives OSCC progression by impairing apoptosis. Its overexpression correlates with poor prognosis and represents a potential diagnostic and therapeutic target. Furthermore, targeting TNFRSF10B may restore apoptosis, thus making precision therapy achievable.