Inflammatory Bowel Disease (IBD) refers to chronic conditions leading to intestinal inflammation and lesions caused by a dysregulated immune response to host intestinal microflora. The current treatments use corticosteroids, anti-inflammatories and antibiotics that are ineffective in the long term. Patients with longer duration and extent of colitis are at increased risk for developing colorectal cancer (CRC). There is often a limit in using chemotherapy due to its side effects. Immune checkpoint inhibitors as single agents and combination regimens have produced durable and long-lasting clinical responses in the field of cancer immunotherapy. Muc2 is an important mucin secreted by goblet cells in the colon and acts as a barrier against toxins and bacterial products. Decreased levels of Muc2 are noted in patients with IBD. A point mutation of the Muc2 gene results in a model of spontaneous chronic colitis, named Winnie mice; older Winnie mice progress to severely inflamed Winnie-prolapse mice. These mice are a viable model to study chronic inflammation and inflammation-induced CRC, with immune changes similar to human chronic colitis. Colon tissues from Winnie, Winnie-Prolapse and C57BL/6 mice were collected. mRNA was extracted and sent for Next Generation Sequencing. Data was analyzed, Gene Ontologies (GO) and KEGG pathways were presented. Upregulated genes were associated with immune system processes and inflammatory pathways. Downregulated genes were mainly involved in nervous system processes. Several cancer-related pathways, cancer genes, and checkpoint markers were upregulated in Winnie-prolapse compared to Winnie mice. These results provide evidence for changes in the colon to pre-cancerous condition depending on the severity of inflammation. Further studies of the checkpoint markers and other cancer-related genes and pathways identified could lead to the development of new biomarkers for IBD and inflammation-induced CRC for drug and vaccine development to prevent disease progression.