Prognostic and therapeutic insights into colorectal carcinoma through immunogenic cell death gene profiling

Abstract

While the significance of immunogenic cell death (ICD) in oncology is acknowledged, its specific impact on colorectal carcinoma remains underexplored. In this study, we delved into the role of ICD in colorectal carcinoma, a topic not yet comprehensively explored. A novel ICD quantification system was developed to forecast patient outcomes and the effectiveness of immunotherapy. Utilizing single-cell sequencing, we constructed an ICD score within the tumor immune microenvironment (TIME) and examined immunogenic cell death related genes (ICDRGs). Using data from TCGA and GEO, we discovered two separate molecular subcategories within 1,184 patients diagnosed with colon adenocarcinoma/rectum adenocarcinoma (COADREAD). The ICD score was established by principal component analysis (PCA), which classified patients into groups with low and high ICD scores. Further validation in three independent cohorts confirmed the model’s accuracy in predicting immunotherapy success. Patients with higher ICD scores exhibited a “hot” immune phenotype and showed increased responsiveness to immunotherapy. Key genes in the model, such as AKAP12, CALB2, CYR61, and MEIS2, were found to enhance COADREAD cell proliferation, invasion, and PD-L1 expression. These insights offered a new avenue for anti-tumor strategies by targeting ICD, marking advances in colorectal carcinoma treatment.

Keywords

• Immunogenic cell death
• Colorectal carcinoma
• Immunotherapy
• Comprehensively analysis