Rnf43 Mutation As A Biomarker For Immune Checkpoint Inhibitor Efficacy In Colorectal Cancer

Abstract

\n Background: Immune checkpoint inhibitors can prolong the survival of patients with advanced colorectal cancer and have been approved for the treatment of metastatic colorectal cancer patients with mismatch repair defects and high microsatellite instability (dMMR-MSI-H). However, there are still many deficiencies in their clinical application, such as their benefit in a limited population, low efficiency, and lack of accurate markers. Therefore, finding accurate biomarkers has become an urgent problem in the immunotherapy of colorectal cancer. Our research aimed to find biomarkers that can accurately predict the population with potential benefit.Methods: We analysed data from a colon cancer immunotherapy cohort (n = 110, ICI cohort), including mutation data and clinical data, to identify the mutated gene closely related to Immune Checkpoint Inhibitors (ICIs). Next, we further verified the relationship between gene mutation and clinical features, such as Tumor Mutational Burden (TMB) and Microsatellite Instability (MSI) status in the TCGA colorectal cancer data set (non-ICI cohort). Then, CIBERSORT was used to analyse the relationships between gene mutation and both immune cell infiltration and immune genes, and GSEA was used to analyse the effect of gene mutation on pathway activation levels. In addition, we analysed the Whole-exome Sequencing (WES) and drug sensitivity data of colorectal cancer cell lines in the GDSC database.Conclusions: Our results show that Rnf43 mut can be used as a biomarker to predict the efficacy of ICI for colorectal cancer, and it can be used for clinical screening of patients who benefit from ICI for colorectal cancer.