MicroRNA Signatures of Colonic Polyps on Screening and Histology

Abstract

Colorectal cancer and adenoma adjacent to cancer exhibit distinct microRNA (miRNA) alterations in an apparent mucosa-to-adenocarcinoma sequence. The pattern of microRNAs in screen-detected polyps in relation to histologic features and cancer risk has not been investigated. miRNA expression analysis was performed on normal mucosa (NM), hyperplastic polyps (HP), tubular adenomas (TA), tubulovillous adenomas or high-grade dysplasia (TVHG), and serrated polyps [sessile serrated adenoma/polyps (SSA/P) and traditional serrated adenomas (TSA)] in biopsy specimens from 109 patients undergoing screening/surveillance colonoscopy. Generalized linear models were used to identify differentially expressed miRNAs by histologic type and logistic regression to identify miRNA predictors of histopathology. False discovery rate (FDR) was used to control for multiple comparisons. We identified 99 miRNAs differing in at least one of five histopathologic groups (FDR ≤0.05). In a comparison of HPNM versus TVHG, the top most upregulated and downregulated miRNAs in HPNM included miR-145, -143, -107, -194, and -26a (upregulated), and miR-663, -1268, -320b, -1275, and -320b (downregulated; FDR P < 0.05). miR-145 and -619 showed high accuracy to discriminate low- from high-risk polyps without serrated histology (TVHG vs. HPNM + TA; CI, 95.6%), whereas miR-124, -143, and -30a showed high accuracy of separating high-risk polyps (TVHG + TSA) from low-risk polyps (HPNM + TA + SSA/P; CI, 96.0%). For TSAs, miR-125b and -199a were uniquely downregulated relative to HPNMs, and miR-335, -222, and -214 discriminated between non-serrated and serrated histology. Our data support the presence of colorectal cancer-associated miRNA alterations in screen-detected adenomas that may be useful for risk stratification for surveillance interval planning. Cancer Prev Res; 9(12); 942-9. ©2016 AACR.

Figure 1

Hierarchical clustering of differentially expressed miRs by histologic type. Clustering was based on the profiling of 99 miR probes (FDR < 0.05). Probe intensity are represented in the columns and the histologic type are presented in the rows. Green indicates highly expressed probes while red indicates probes with low expression. Histologic types are annotated as hyperplastic polyp or normal mucosa (HPNM), tubular adenoma (TA), sessile serrated adenoma polyp (SSA/P), traditional serrated adenoma (TSA), any tubulovillous or villous adenoma (TV), and high-grade dysplasia (HG).

Figure 2

Scatterplot illustrating canonical discriminant analysis findings for 99 miRs across five histologic groups. Histologic types are annotated as hyperplastic polyp or normal mucosa (HPNM), tubular adenoma (TA), sessile serrated adenoma polyp (SSA/P), traditional serrated adenoma (TSA), and any tubulovillous or villous adenoma or high-grade dysplasia (TVHG).