RNA editing is the potential biomarker for carcinogenesis of Crohn's disease

Background: Crohn's disease is one of inflammatory bowel disease alongside ulcerative colitis. In Crohn's disease, the major clinical concerns include fibrotic strictures of the ileum and carcinogenesis in the lower rectum and anus. Crohn's disease is associated with higher risk of carcinogenesis than the general population. However, the mechanisms driving carcinogenesis in Crohn's disease remain poorly understood. We recently reported that ADAR1‐mediated RNA editing can mark carcinogenesis in ulcerative colitis. In this study, we therefore examine the potential role of ADAR1 in Crohn's disease‐associated cancer. Methods: A single-center retrospective study was conducted on 51 Crohn's disease patients who underwent colorectal resection of at our hospital in 2008-2023. There were 46 non-cancer tissue and five rectal cancer tissue. The expression level of ADAR1 protein was analyzed by immunohistochemistry (IHC) in FFPE samples with immunoreactive score. In vivo, we established AOM/DSS carcinogenesis model mouse. ADAR1 expression and RNA editing level were analyzed by IHC and RT-qPCR. Results: ADAR1 expression levels were significantly elevated in cancer tissues compared to non-cancer tissues (p < 0.05) in colorectal epithelial cells. In addition, ADAR1 expression was upregulated at both the transcriptomic levels (p = 0.0308) and protein levels (p <0.05) in the colorectal epithelial tissues of model mouse. Furthermore, the AZIN1 RNA editing ratio was significantly increased in colorectal tissues of model mouse as determined by RESSq-PCR (p = 0.043). Conclusion: In this study, elevated expression of RNA editing enzymes has been observed in cancer tissues of Crohn's disease. A similar result was also observed in colorectal epithelial cells of colitis and carcinogenesis model mouse. These findings suggest that continued research may help establish ADAR1 as a potential biomarker and treatment target in inflammatory bowel disease.