P215 Mir-135b, an Early Biomarker of Sporadic and IBD-Related Colorectal Carcinogenetic Progression

Abstract

Abstract Background Although the rates of IBD-related-CRC are decreasing over time, CRC is still a leading cause of mortality and reason for colectomy in patients with IBD. Among the different cancer biomarkers, microRNAs (miRs) have emerged as noninvasive tools for diagnosis, monitoring, and prognosis in tissues and biofluids of patients with IBD. Therefore, we aimed to investigate the role of miRs in the development and natural course of IBD-related CRC, in order to identify potential early biomarkers for IBD-related CRC screening and progression. Methods The cases were retrospectively collected from the archives of the Surgical Pathology and Cytopathology Unit at the University of Padua. We analysed 9 miRs in colonic tissue specimens of IBD patients with adenoma or dysplasia, with IBD related-CRC, other than 2 control groups of patients with sporadic CRC and of healthy subjects (HC). In addition, we included tissue samples from a colonoscopy that patients with IBD with adenoma or dysplasia underwent some years before the development of mucosal lesions (from 2 to 5 years before), therefore without evidence of adenoma or dysplasia. Results were analyzed with ThermoFisher Connected™ Software and a p-value < 0.05 was considered significant. Results Compared to HC, all nine analysed miRs were significantly up-regulated in patients with sCRC, with IBD-related CRC and in IBD patients with adenoma. While, only 3 miRs (miR-135b, mir-21, miR-224) were significantly upregulated in IBD patients with dysplasia (and in their own controls) compared to HC (p<0.0001). Notably, no differences in miRs expression levels were found in patients with IBD-related CRC compared to those found in patients with sCRC. Among all miRs analyzed, only miR-135b and miR-21 resulted significantly up-regulated in patients with IBD. Considering the levels of miR-135b in the tissue samples of IBD patients, we observed an evident increasing trend going from tissue specimens without lesions to those with adenoma or dysplasia and then to those with neoplastic lesions. miR-21 was significantly upregulated in patients with IBD-related CRC compared to both IBD patients with adenoma and their own control samples from a previous negative colonoscopy (p=0.003 and p=0.006, respectively). Likewise, a significant difference in miR-21 levels was observed between patients with IBD-related CRC and those with dysplasia (p=0.02). Conclusion miR-21 and miR-135b are involved in the carcinogenesis process of patients with IBD. They could be potential candidate biomarkers for diagnostic purpose, prognostic and predictive stratification of patients.