Background: Increasing evidence has depicted that DNA repair-related genes (DRGs) are associated with the prognosis of colorectal cancer (CRC) patients. Thus, the aim of this study was to evaluate the impact of DNA repair-related gene signature (DRGS) in predicting the prognosis of CRC patients.
Method: In this study, we retrospectively analyzed the gene expression profiles from six CRC cohorts. A total of 1,768 CRC patients with complete prognostic information were divided into training cohort (n=566) and 2 validation cohorts (n=624 and 578, respectively). LASSO-Cox model was applied to construct a prediction model.
Results: Among 1,376 DRGs, a prognostic DRGS consisting of 11 distinct genes stratified patients into high and low -risk groups. In all cohorts, patients in the high -risk groups had significantly worse disease-free survival (DFS) compared with those in the low-risk groups (training cohort: hazard ratio (HR) = 2.40, 95% confidence interval (CI) = 1.67-3.44, P < 0.001; validation-1: HR = 2.20, 95% CI = 1.38-3.49, P < 0.001; validation-2 cohort: HR = 2.12, 95% CI = 1.40-3.21, P < 0.001). After adjusting for clinical features and molecular types, DRGS still remained as an independent prognostic marker in multivariable analysis (training cohort: HR = 1.80; 95% CI = 1.22-2.64, P = 0.0028; validation-1: HR = 1.85, 95% CI = 1.13-3.02, P = 0.015; validation-2 cohort: HR = 1.75, 95% CI = 1.15-2.65, P = 0.0085). Gene Set Enrichment Analysis (GSEA) showed significant dysregulated pathways in the high-risk involved in angiogenesis, KRAS signaling, epithelial mesenchymal transit (EMT) and myogenesis (P < 0.001).
Conclusions: DNA repair-related gene signature is a favorable prognostic model for patients with CRC, and further studies are necessary to validate the exact biological mechanism.