Jun Xiang1#, JunHu Li2#, XiaoNan Cheng3, HanQing Hu1, Lei Yu1*, GuiYu Wang1*
Background: Since Food and Drug Administration (FDA) approved immune checkpoint inhibitors for the treatment of colorectal cancer in 2017, there have been significant differences in the response of colorectal cancer patients to immune checkpoint inhibitors. In order to achieve better clinical benefits of colorectal cancer patients in immunotherapy, we urgently need to find a biomarker to evaluate whether colorectal cancer patients respond to immunotherapy. In this research, we aimed to explore a biomarker to predict the efficacy of immunotherapy for colorectal cancer patients.
Materials and methods: We collected the expression profiles and clinical information of more than 1800 colorectal cancer patients in 6 cohorts in Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases and meanwhile, we collected 230 immune related signatures by searching literatures. Single sample gene set enrichment analysis was performed on 230 signatures, and the normalized enrichment score of each patient was calculated. Then, the Immune Related Prognosis Score (IRPS) was constructed based on normalized enrichment scores. Finally, an extensive analysis was performed to explore the relationship between the IRPS and immune score, prognostic significance, microsatellite status, immunogenomic factors, cancer genotype and potential immune escape mechanism.
Results: We found that the IRPS can reflect the immune infiltration status of colorectal cancer patients, and it is related to some important immunophenotypic factors, such as neoantigen load and Tumor Mutational Burden (TMB). Further analysis confirmed that patients with the low IRPS had a better response to immune checkpoint inhibitors.
Conclusion: Based on these results, we can conclude that the IRPS may be an available tool for the prediction of immunotherapy efficacy in colorectal cancer patients.