OBJECTIVE: To evaluate the clinical significance of HMGA2 expression and its association with oncogenic signaling pathways in oral squamous cell carcinoma (OSCC). METHODS: RNA-seq data and clinical information of OSCC patients (n=253) and normal oral tissues (n=27) were obtained from The Cancer Genome Atlas (TCGA). HMGA2 expression was compared between normal oral tissues and OSCC tissues, and patients were stratified into HMGA2-high and HMGA2-low groups based on median expression. Differentially expressed genes were identified using DESeq2, followed by pathway enrichment analyses using Reactome and WikiPathways. Functional validation was independently performed in two OSCC cell lines using siRNA-mediated HMGA2 knockdown. Cell proliferation, colony formation, and migration were assessed, and EGFR signaling and EMT-related proteins were analyzed by Western blotting. RESULTS: HMGA2 expression was significantly higher in OSCC tissues than in normal oral tissues (adjusted p < 0.001) and was associated with advanced AJCC stage and poorer overall survival (p < 0.05). Pathway analyses revealed significant enrichment of EGFR-related signaling and epithelial-mesenchymal transition (EMT)-associated processes in the HMGA2-high group. HMGA2 knockdown significantly reduced proliferation, clonogenicity, and migration of OSCC cells, accompanied by decreased expression of mesenchymal markers and reduced activation of EGFR and its downstream effectors, including AKT, ERK, and STAT3. EGFR pathway activity was partially restored by exogenous EGF treatment. CONCLUSION: HMGA2 overexpression is associated with poor prognosis in OSCC and functions as both a prognostic biomarker and a functional contributor to aggressive tumor behavior through EGFR-associated signaling and EMT-related phenotypes.
Wu et al. (Fri,) studied this question.