Associations between Markers of Colorectal Cancer Stem Cells, Mutations, Mirna, and Clinical Characteristics of Ulcerative Colitis

Background: Several factors have been implicated in the pathogenesis of colorectal cancer (CRC) associated with ulcerative colitis (UC). We investigated markers of cancer cell pluripotency, including CD44 and CD166, microRNA-21 (miR-21) and microRNA-215 (miR-215), and APC, K-ras and DCC mutations in biopsy specimens from patients with UC to evaluate any correlations with clinical risk factors. Methods: We observed 18 patients with UC and collected two biopsy specimens from each patient at diagnosis and at a follow-up endpoint. We examined the expression of CD44, CD166, miR-21 and miR-215 as well as APCKras and DCC mutations. We compared these markers from the two points in time and assessed their associations with clinical characteristics, including colitis duration, histological alterations, and patient age at UC onset. Results: Most patients (16/18) had attenuated colonic lesions or remained stable during follow-up, except one patient who developed dysplasia, and one who had severe lesion aggravation during follow-up. Enhanced expression of CD44, CD166 and miR-21 with miR-215 was found in the specimens obtained at follow-up, despite attenuation of mucosal lesions. Coherence of cancer stem cell markers and microRNAs was seen in patients who had significant aggravation of mucosal alteration, dysplasia, and long duration of colitis. APC mutation occurred in only one patient, who had the longest duration of UC (23 years). Conclusion: Enhanced markers of CRC in the follow-up colon samples support our conclusion that UC duration plays the most important role in UC-related carcinogenesis.