The correlation of ferroptosis and DNA repair in individuals with colorectal cancer

Abstract

Abstract Crosstalk between ferroptosis and DNA repair is shown in various human illnesses, including malignancies. This study aims to develop a prognostic signature, using ferroptosis and DNA repair-related gene (DRFG), to forecast the prognosis and therapeutic responsiveness of colorectal cancer (CRC) patients. 34 DRFGs related to oxidative stress and ferroptosis were identified. Bioinformatics analysis, utilizing expression profiles of these genes and clinical data, categorized CRC patients into two DRFG clusters, revealing differentially expressed genes (DEGs) and associations with patient survival and immune cell infiltration. Risk scores based on prognosis-linked genes in both clusters were used to construct prognostic signatures. Low-risk patients demonstrated better outcomes, increased immune cell infiltration, and improved responses to chemotherapy and immune checkpoint blockade compared to high-risk patients. These results were successfully validated across multiple independent datasets, suggesting that low-risk CRC could be considered a hot tumor, while high-risk CRC is a cold tumor. The study also verified the expression levels of 6 characteristic genes in CRC and adjacent normal tissues to identify potential biomarkers. In conclusion, the study identified 34 DRFGs and developed a prognostic signature, demonstrating its efficacy in predicting survival and treatment response in CRC patients. These results hold promise for guiding precise treatment strategies in clinical practice and distinguishing between cold and hot tumors in CRC.