ATP6V0A4 as a novel prognostic biomarker and potential therapeutic target in oral squamous cell carcinoma.

BACKGROUND: Increasing evidence indicates that the dysregulation of ATP6V0A4 is linked to aggressive behaviors in various types of cancer. Nevertheless, the exact role and molecular mechanisms of ATP6V0A4 in oral squamous cell carcinoma (OSCC) are not yet fully understood. METHODS: This study initially integrated TCGA and GEO databases for cross-platform differential gene screening. A prognostic model was constructed using univariate Cox regression and LASSO regression, complemented by random forest algorithms to identify core genes. Subsequently, a multi-omics analysis strategy was employed, systematically conducting pan-cancer expression profiling, human protein atlas validation, GO/KEGG enrichment analysis, clinicopathological feature correlation analysis, and tumor immune microenvironment assessment. Further, immunotherapy response prediction models and drug sensitivity analysis were utilized to define therapeutic potential. For experimental validation, RT-qPCR was performed to measure ATP6V0A4 expression in OSCC cell lines, and plasmid transfection technology was used to establish overexpression models, followed by systematic evaluation of its regulatory effects on tumor cell proliferation, migration, and invasion. RESULTS: Our findings reveal that low expression of ATP6V0A4 is significantly associated with poor prognosis in patients with OSCC. Moreover, the expression level of ATP6V0A4 shows a close correlation with clinical T staging. Further investigations demonstrate that the expression status of ATP6V0A4 is significantly associated with the distribution and function of follicular helper T cells, regulatory T cells, naive B cells, resting dendritic cells, and natural killer cells. Results from in vitro cell experiments indicate that overexpression of ATP6V0A4 can significantly suppress the proliferation, migration, and invasion capabilities of OSCC cells. Notably, OSCC patients with low ATP6V0A4 expression exhibit higher sensitivity to drugs such as GDC0810, GSK591, and MK8776. This discovery provides novel insights and potential strategies for the development of combination therapy regimens for OSCC. CONCLUSIONS: ATP6V0A4 may serve as a novel prognostic biomarker and potential therapeutic target in oral squamous cell carcinoma.