The presence of checkpoint markers in cancer cells aids in immune escape. Chronic inflammation is a key driver of oncogenesis, and inflammatory bowel disease (IBD) is strongly associated with the development of cancer. 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. In this study, the Winnie mouse model of chronic colitis is used to show that the severity of inflammation leads to the expression of a wide range of cancer genes. The differential gene expression of checkpoint makers, cancer-related pathways, and cancer genes in colon tissues of mouse models of spontaneous chronic colitis (Winnie and Winnie-Prolapse) are determined by sequencing the RNA using next-generation sequencing. 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 analyzed based on the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway. The expression of several oncogenes is associated with the severity of IBD, with chronic colitis mouse models expressing many key genes associated with development of cancer. This research presents a number of new targets to evaluate for the development of biomarkers and therapeutics.