Constructing a prognostic model for colon cancer patients on basis of coagulation genes enriched in cancer-associated fibroblasts to guide personalized immunotherapy

Abstract

Abstract Objectives Colon cancer is a global health challenge. This research is designed to build a prognostic model that can personalize the guidance of immunotherapy among colon cancer patients. Methods Coagulation-associated prognostic genes which were subsequently integrated into a Least Absolute Shrinkage and Selection Operator algorithm for constructing a prognostic model were identified with the univariate Cox analyses. The potential of coagulation-related risk score (CRRS) in prognosis and immunotherapy outcomes was rigorously assessed. Finally, the cellular origin of genes in the CRRS model was explored with single-cell RNA-seq data, and the biological functions of core genes were further confirmed by cell function experiments. Results Our findings showed the CRRS model usefully classified patients into high-risk and low-risk groups. High-risk patients exhibited worse total survival. A nomogram was subsequently devised, enabling quantitative survival prediction by incorporating CRRS, age, sex, and TNM stage. Moreover, the CRRS model predicted the extent of cancer-associated fibroblasts (CAFs) infiltration. The analysis further indicated diminished immune responsiveness in high-risk patients, and single-cell data analysis pinpointed TIMP1+ CAF as a potential contributor to cancer progression. Conclusions The CRRS model can be adopted as a prognostic device for colon cancer patients and low-risk patients are more suitable for treatment with immune checkpoint inhibitors. TIMP1 secreted by CAF can promote the malignant progression of colon cancer.