Identification of super-enhancer-based biomarkers for predicting survival and immunotherapy efficacy in colorectal cancer.

Immune checkpoint inhibitors are effective treatments for many tumors. However, existing biomarkers can benefit only a small selection of colorectal cancer patients. Super-enhancers are associated with various tumor characteristics. We wondered whether super-enhancer-related genes could be novel biomarkers for immunotherapy. We screened super-enhancer-related genes that were highly correlated with immune infiltration through weighted gene co-expression network analysis on the basis of chromatin immunoprecipitation sequencing data. A prognostic risk signature was established using least absolute shrinkage and selection operator and cox regression models. By analyzing the correlations between the expression of model genes and the immunophenotypic and microsatellite instability scores, we determined that PLAU and GSDMC expression had high predictive value for immunotherapy efficacy. Moreover, we predicted the sensitivity of the PLAU and GSDMC proteins to drugs by virtual docking. Finally, we validated the effect of the super-enhancer activity on PLAU and GSDMC expression. Overall, our study identified super-enhancer-based biomarkers for predicting survival and immunotherapy efficacy in colorectal cancer.