A ferroptosis associated gene signature for predicting prognosis and immune responses in patients with colorectal carcinoma

Background: Colorectal carcinoma (CRC) is one of the most prevalent malignancies globally. Ferroptosis, a novel type of cell death, is critical in the development and treatment of tumors. Objective: This study was designed to establish a genetic signature for ferroptosis which has a predictive effect on the outcomes and immunotherapeutic response of CRC. Methods: Data of CRC patients were retrieved from TCGA and GEO databases. The genes associated with ferroptosis were obtained from GeneCards. The genetic signature for ferroptosis was identified by performing Cox regression analysis. Kaplan-Meier and ROC analysis were performed to assess the prognosis role of the genetic signature. CIBERSORT tool was used to identify a potential association of the genetic signature with the immune cells. The potential immunotherapeutic signatures and drug sensitivity prediction targeting this signature were also discussed. Immunohistochemistry was used to detect expression of ferroptosis-associated genes in CRC tissues and adjacent tissues. Results: A ferroptosis-associated gene signature comprised of three genes (CDKN2A, FDFT1, and ACSL6) was developed for prediction of prognosis and evaluation of immune responses in CRC. Patients in the high-risk group tended to have a poor prognosis. In CRC, the ferroptosis-associated gene signature may function as independent predictors. Additionally, the expressional levels of the immune checkpoint proteins PD-L1 and CTLA-4 were substantially increased in the high-risk group. Moreover, we can distinguish between patients based on their immunotherapeutic responses more effectively if we categorize them by this signature. Additionally, candidate compounds were identified for the differentiation of CRC subtypes. Conclusion: The ferroptosis-associated gene signature identified in this study is effective in predicting the prognosis and evaluating immunotherapeutic response in CRC patients, and provides us with novel insights into the potential effect of ferroptosis targeted treatment on CRC.