Association of immune-related gene DNA methylation patterns with tumor progression in colorectal cancer: a clinical...

To evaluate the prognostic value and clinical use of plasma-derived immune gene DNA methylation patterns in colorectal cancer (CRC).

A total of 300 patients with pathologically confirmed CRC (2021-2023) and 100 healthy controls were retrospectively enrolled. Methylation levels of programmed death-ligand 1 (PD-L1), cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), interferon regulatory factor 1 (IRF1), and forkhead box protein P3 (FOXP3) were measured using methylation-specific quantitative polymerase chain reaction (MSP). An integrated methylation risk score (IMRS) was developed using a logistic regression model. The associations between IMRS and clinicopathologic characteristics were analyzed. All patients were followed up for 24 months postoperatively. The prognostic performances of IMRS and carcinoembryonic antigen (CEA) for recurrence-free survival (RFS) were evaluated and compared using Kaplan-Meier and Cox regression analyses.

CRC patients exhibited a markedly elevated IMRS compared to controls (P < 0.001). Elevated IMRS was significantly correlated with advanced Tumor-Node-Metastasis (TNM) stage (P = 0.002), lymph node metastasis (P = 0.005), and distant organ metastasis (P = 0.001). Survival analysis revealed a 2-year RFS rate of 54.0% in the high-IMRS patients, significantly lower than 88.0% in the low-IMRS cohort (Log-rank P < 0.001). After adjustment for TNM stage, CEA, and other confounders, multivariate Cox regression analysis identified high IMRS as an independent predictor of poorer RFS (hazard ratio (HR) = 2.81, 95% confidence interval (CI): 1.88-4.20). The predictive value of IMRS (C-index = 0.79) outperformed TNM stage, preoperative CEA, and individual gene methylation markers.

The IMRS, derived from circulating immune gene methylation, independently predicts aggressive clinicopathological features and unfavorable prognosis in CRC, highlighting its potential as a noninvasive biomarker for postoperative risk stratification.