Differential Gene Expression of Checkpoint Markers and Cancer Markers in Mouse Models of Spontaneous Chronic Colitis

SIMPLE SUMMARY: Chronic inflammation is a key driver of oncogenesis, and inflammatory bowel disease is strongly associated with the development of cancer. In this study, the Winnie mouse model of inflammatory bowel disease is used to show that the severity of inflammation leads to the expression of a wide range of cancer genes. This study provides important insights into the genetic basis for malignancy in inflammatory bowel disease, as well as identifying markers that could be used to screen for the development of cancer in patients. ABSTRACT: The presence of checkpoint markers in cancer cells aids in immune escape. The identification of checkpoint markers and early cancer markers is of utmost importance to gain clarity regarding the relationship between colitis and progressive inflammation leading to cancer. Herein, the gene expression levels of checkpoint makers, cancer-related pathways, and cancer genes in colon tissues of mouse models of chronic colitis (Winnie and Winnie-Prolapse mice) using next-generation sequencing are determined. Winnie mice are a result of a Muc2 missense mutation. The identification of such genes and their subsequent expression and role at the protein level would enable novel markers for the early diagnosis of cancer in IBD patients. The differentially expressed genes in the colonic transcriptome were analysed based on the Kyoto Encyclopedia of Genes and Genomes pathway. The expression of several oncogenes is associated with the severity of IBD, with Winnie-Prolapse mice expressing a large number of key genes associated with development of cancer. This research presents a number of new targets to evaluate for the development of biomarkers and therapeutics.