COL11A2 Methylation as a Biomarker for Radiosensitivity and Microenvironment Remodelling in Oral Squamous Cell Carcinoma.

BACKGROUND

Given that DNA methylation and the tumour microenvironment (TME) are both key contributors to tumour radiosensitivity, we aimed to identify specific differential DNA methylation patterns associated with oral squamous cell carcinoma (OSCC) prognosis and TME changes after radiation.

METHODS

Differential methylation analysis was conducted using the Tissue Cancer Genome Atlas database (TCGA). Differential methylation positions (DMPs) and differentially methylated regions (DMRs) were identified between normal oral tissue and OSCC tissue. For screening and validating differentially methylated genes, interaction analysis, Kaplan-Meier (K-M) survival curves, Cox proportional hazards models, and linear regression were performed. Spline smoothing was used to analyse the correlation between XI collagen alpha-2 chain (COL11A2) methylation and overall survival post-radiotherapy. CIBERSORT and ESTIMATE algorithms were used to correlate COL11A2 methylation with immune infiltrates, following GSEA analysis to evaluate biological processes.

RESULTS

COL11A2 was identified from the top 10 DMPs and DMRs intersection. COL11A2 methylation showed a nonlinear relationship with OSCC survival, with two inflection points at β = 0.23 (P = .3430) and β = 0.35 (P = .0520). The K-M curve showed that COL11A2 methylation was negatively correlated with OSCC survival (P = .0458). The diagnostic association map revealed that radiotherapy was correlated with OSCC prognosis (P = .0202), with high methylation linked to better outcomes. High COL11A2 methylation was associated with increased immune cell infiltration, such as CD4+ T cells, CD8+ T cells, and NK cells. Enrichment analysis using DAVID identified the Hippo signalling pathway (P = .00001), TRP (P = .00014), and HPV signalling pathways (P = .00022) as significantly associated with COL11A2 methylation.

CONCLUSION

COL11A2 methylation level shows promise as a predictor for post-radiotherapy prognosis in OSCC, potentially through its influence on immune cell infiltration and key signalling pathways. Further experiments are needed to confirm its role and mechanism.