Integrative transcriptomic analysis identifies shared coding and non-coding biomarkers in tongue squamous cell carcinoma across diverse populations

BACKGROUND: Tongue cancer, a prevalent subtype of oral malignancy, remains a significant global health burden with high morbidity and mortality, particularly in developing countries. Understanding its molecular landscape is crucial for developing targeted diagnostics and therapeutics. OBJECTIVE: This systematic review aimed to identify common differentially expressed protein-coding genes (DEGs) in tongue cancer across multiple populations and explore their functional significance through integrative bioinformatic analyses. METHODS: We performed an integrative meta-analysis of transcriptomic datasets from China, the USA, and Australia to identify common differentially expressed genes (DEGs). Functional enrichment, protein-protein interaction (PPI), and regulatory network analyses were conducted. Crucially, the clinical relevance of identified hub genes was validated using the TCGA-HNSC cohort to assess correlations with tumor stage and overall survival. RESULTS: A total of 133 common DEGs were identified, primarily enriched in extracellular matrix (ECM) disassembly, collagen catabolism, and IL-17 signaling. Key hub genes included MMP3, MMP10, COL1A1, CDKN2A, and CXCL11. Network analysis uncovered novel lncRNAs, including TENM3-AS1 and DUXAP10, regulating immune and epithelial pathways. Clinical validation demonstrated that high expression of STC2 and MMP3 significantly correlated with advanced tumor stage (p < 0.05). Furthermore, STC2 upregulation was identified as a significant predictor of poor overall survival (p = 0.0037). CONCLUSION: This study defines a cross-population gene signature driving TSCC through ECM remodeling and immune modulation. The validation of STC2 as a prognostic marker highlights its potential for clinical risk stratification.