ArticleTranslational oncology2026
Identification and functional validation of a four-gene signature associated with radiotherapy resistance in oral squamous cell carcinoma.
Article in Translational oncology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Radiotherapy resistance remains a major obstacle in the treatment of oral squamous cell carcinoma (OSCC). This study aimed to identify radiotherapy-associated prognostic biomarkers and explore their functional relevance in OSCC. Integrated single-cell RNA-seq analysis, TCGA-based bulk transcriptomic analysis, Scissor analysis, hdWGCNA, and random survival forest modeling identified a four-gene risk signature comprising KPNA2, P4HA1, ARL6IP1, and TUBA1B. The model effectively stratified patients into high- and low-risk groups and showed prognostic value in both the TCGA-OSCC training cohort and the GSE41613 validation cohort. Immune infiltration, immune checkpoint, malignant subclustering, pseudotime, CellChat, and virtual knockout analyses further suggested that these genes were associated with tumor immune remodeling, malignant cell heterogeneity, oxidative stress, ferroptosis, and extracellular matrix-related pathways. Immunohistochemical validation showed that KPNA2, P4HA1, ARL6IP1, and TUBA1B were upregulated in OSCC tissues, particularly in radioresistant OSCC tissues. In vitro, HSC-3 and SCC9 cells exhibited relatively stronger radioresistance, and siRNA-mediated knockdown of these genes in SCC9 cells enhanced irradiation-induced suppression of metabolic activity, colony formation, and invasion. Collectively, these findings suggest that KPNA2, P4HA1, ARL6IP1, and TUBA1B may serve as prognostic biomarkers and potential therapeutic targets for overcoming OSCC radioresistance.
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