Increased expression of mitochondrial enzyme MTHFD2 associated with clinicopathological features and prognosis of oral squamous cell carcinoma

Background This study investigated the expression profile of MTHFD2 at both transcript and protein levels in oral squamous cell carcinoma (OSCC). In addition, its association with clinicopathological parameters, patient survival, and immune-related features was systematically evaluated. Methods Publicly available transcriptomic data from The Cancer Genome Atlas were analyzed to assess MTHFD2 expression in OSCC, followed by experimental validation in an independent cohort of 42 OSCC patients. Quantitative real-time PCR was employed to validate MTHFD2 transcript expression in OSCC tissues. Protein-level expression patterns were evaluated using publicly available immunohistochemistry datasets from the Human Protein Atlas and UALCAN, and were not experimentally validated in our independent OSCC cohort. Correlations between MTHFD2 expression and clinicopathological characteristics, overall survival, immune modulation, and functional pathways were further explored using bioinformatic approaches. Results Both mRNA and protein expression levels of MTHFD2 were significantly elevated in OSCC tissues compared with adjacent non-tumor counterparts. Increased MTHFD2 expression was significantly associated with adverse clinicopathological features and poorer survival outcomes in OSCC patients. Protein interaction network analysis revealed that MTHFD2 interacts with multiple oncogenic signaling pathways. Functional enrichment analyses indicated a strong link between MTHFD2-associated networks and biological processes relevant to OSCC initiation and progression. Conclusions Elevated MTHFD2 expression is closely linked to aggressive disease behavior and unfavorable prognosis in OSCC. Its integration within oncogenic signaling pathways and interaction with critical cancer-associated proteins suggest that MTHFD2 may serve as a potential biomarker associated with disease progression. Further functional studies are required to determine its biological and clinical significance.