CpG Island Methylator Phenotype(CIMP) is An Independent Prognostic Marker with Tumor-Promoting Functions in Colorectal Cancer

Abstract

BackgroundThe CpG island methylator phenotype(CIMP)with extensive promoter methylation isa distinct epigenotype incolorectal cancer (CRC). Changes in microbiota and epigenetic dysregulation mightbe the key underlying mechanism.MethodsTissueswith stages I–III cancerwere collected afterproctocolectomy. The 16S rRNA gene sequencing was carried to determine the differences in microbiota.Subsequently,BRAF mutation,the statusof microsatellite instability (MSI, also known as mismatch repair deficiency) and CIMP were also tested. The Chi-square test was carriedoutto analyze the relationship between molecular changes (MSI and CIMP) and the development of CRC.ResultsPatients in the three groups differed in thetumorlocation(P=0.034) and the carcinoembryonic antigen (CEA) level (P=0.036).The positive CIMP and MSI-LOW/MSS were more common in the worse prognosis groups.The Kaplan–Meier and Cox proportional regression analyses indicated that CIMP and MSI were the independent indicators of poor survival since the positive rates of which were significantly higher in the non-survival group. Besides, there were differences in microbiota among tumor tissues of different prognoses, with the Fusobacterium nucleatum and Bacteroides fragilis more abundant in the worse prognosis groups.ConclusionThe persistent epigenetic changes influence the prognosis of patients with CRC and the composition of the gut microbiota might be the cause.