Immunogenic cell death (ICD), a type of cell death that activates the
tumor-specific immune response and thus exerts anti-
tumor effects, is an emerging target in
tumor therapy, but research on ICD-related genes (ICDGs) in
colorectal cancer (CRC) remains limited. This study aimed to identify the CRC-specific ICDGs and explore their potential roles. Through
RNA sequencing for tissue samples from CRC patients and integration with The
Cancer Genome Atlas (TCGA) data, we identified 33 differentially expressed ICDGs in CRC. We defined the ICD score based on these genes in single-cell data, where a high score indicated an immune-active microenvironment. Additionally, molecular subtypes identified in bulk
RNA data showed distinct immune landscapes. The ICD-related signature constructed with machine learning effectively distinguished patients' prognosis. The summary data-based Mendelian randomization (SMR) and colocalization analysis prioritized CFLAR for its positive association with CRC risk. Molecular docking revealed its stable binding with chemotherapeutic drugs like
irinotecan. Furthermore, experimental validation confirmed CFLAR overexpression in CRC samples, and its knockdown inhibited
tumor cell proliferation. Overall, this study expands the understanding of the potential roles and mechanisms of ICDGs in CRC and highlights CFLAR as a promising target for CRC.