Comparative Segmental Assessment of the Colonic Mucosa in Villous Adenomas

Abstract

to identify the frequency of occurrence of solitary nonvillous adenomas in different parts of the large intestine (LI) and to compare segmental expression profiles of 9 genes and 9 microRNAs (miRNAs) in solitary nonvillous adenomas and in the mucosa (MM) of the index segment of the LI and in the unchanged MM of the similar segment of the LI in patients without adenomas.

A continuous retrospective study of the results of 3086 colonoscopies in 2019–2020 and a prospective study (2022–2023) of the index segment of the colon in 111 patients with nonvillous adenomas were conducted. Biopsies from each section of the colon were used to prepare smears and histological assessment. The relative expression levels of 9 miRNAs — markers associated with the development of colorectal cancer (CRC) — were determined in the smears: miRNA-135b-5p, -141-3p, -143-3p, -200a-3p, -20a-5p, -21-5p, -31-5p, -34a-5p, -92a-3p; small nuclear RNA U6, as well as miRNA-16-5p and -191-5p, were used as a reference for them. In addition to miRNA, mRNA of the following genes was used as markers in this work: MUC2, CDX2, NOX1, LGR5, SMAD4, MS4A12, TIMP1, Ki-67, TERT with normalization to the housekeeping genes PGK1 and PUM1. A total of 372 cell samples were examined in this work (adenomas - 92, index segment CO - 111, normal CO - 169).

In the structure of the detected single tumors, nonvillous adenomas prevailed, but the frequency of adenomas by intestinal segments differed significantly (χ2=17.6, p<0.001). The frequency and types of somatic mutations in the BRAF, KRAS genes, as well as the status of microsatellite instability (MSI/MSS) differed by intestinal segments (χ2=6.0, p=0.014). When pairwise comparing the expression of miRNA/mRNA, no differences were found between the SO of the index segments of the intestine and the normal SO. The expression of protein-coding genes (LGR5, TIMP1, MS4A12, Ki-67) had different directions by intestinal segments, but the changes were the same for SO with and without adenomas, with the exception of the cecum and rectum.

significant differences were revealed both in the frequency of single nonvillous adenomas in the TC segments and in the frequency of mutations in them. However, a comparison of the SO of the index segments with similar SO segments without adenomas in terms of somatic mutations and microsatellite instability revealed the same SO, with the exception of the cecum and rectum. Our data do not coincide with the accepted theory of adenomas as precursors to CRC.