CXCL10 as a migration-associated biomarker in oral squamous cell carcinoma.

BACKGROUND

Oral squamous cell carcinoma (OSCC) is marked by aggressive local invasion and early metastasis, yet molecular biomarkers linked to tumor cell motility remain insufficiently defined. CXCL10, an interferon-inducible chemokine, exhibits context-dependent roles across cancers, but its functional relevance to OSCC migration has not been fully elucidated.

METHODS

Three GEO transcriptomic datasets (GSE13601, GSE160042, GSE227919) were analyzed to identify differentially expressed genes (DEGs). Functional enrichment, STRING–Cytoscape protein–protein interaction analysis, and CytoHubba/MCODE were used to prioritize hub genes. A random-effects meta-analysis quantified the pooled expression differences of key candidates. CXCL10 expression was validated using UALCAN, CPTAC, and an independent OSCC tissue microarray. The functional role of CXCL10 was examined via siRNA-mediated knockdown and recombinant CXCL10 treatment in HSC3 and SCC4 cell lines using wound-healing and Transwell migration assays.

RESULTS

A total of 263 overlapping DEGs were identified across the three cohorts, enriched in pathways related to extracellular matrix organization, focal adhesion, immune regulation, and antiviral responses. Network analyses identified five hub genes, among which CXCL10 demonstrated the highest pooled overexpression in OSCC (log₂FC = 4.27; 95% CI 2.02–6.52). UALCAN and CPTAC analyses confirmed elevated CXCL10 transcript and protein levels in tumor tissues, which were further validated by tissue-array immunohistochemistry. Functionally, CXCL10 knockdown significantly reduced OSCC cell migration, whereas recombinant CXCL10 dose-dependently enhanced motility.

CONCLUSIONS

CXCL10 is markedly overexpressed in OSCC and contributes to tumor cell motility in vitro. These findings support CXCL10 as a migration-associated candidate biomarker with potential clinical relevance, warranting further validation in OSCC cohorts.