Comparative characteristics of the transcriptional activity of CDH1, CTNNB1 genes and the expression levels of E-cadherin, β-catenin proteins, coded by these genes, in intestinal-type gastric adenocarcinoma

V A Tumanskiy,T A Khrystenko

doi:10.14739/2310-1237.2017.1.97490

Abstract

Molecular genetics abnormalities, underlying aberrant expression of E-cadherin and β-catenin in malignant tumors, are still unclear. Aim: to compare the mRNA expression levels of CDH1 and CTNNB1 genes and the immunohistochemical expression levels of E-cadherin and β-catenin proteins in intestinal-type gastric adenocarcinoma. Materials and methods. The molecular genetic (real-time PCR) and immunohistochemical studies of the intestinal-type gastric adenocarcinoma (30 patients; I, II and III clinical stages were included) and of the normal stomach mucosa (10 samples) were conducted. Results. In comparison with the normal stomach mucosa, the intestinal-type gastric adenocarcinoma differs by the reduced transcriptional activity of the CDH1 gene [Me of relative normalized ratio of mRNA expression level is 0.14 (0.03; 0.40)], which correlates with the low expression level of E-cadherin in cancer cells [Me is 27,59 CUOD (23,14; 37,19), Spearman's correlation coefficient = 0,73], and also by the heightened transcriptional activity of the CTNNB1 gene [Me of relative normalized ratio of mRNA expression level is 4.32 (2.11; 11.43)], which correlates with the high expression level of β-catenin in cancer cells [Me is 116.65 CUOD (110.34; 151.32), Spearman's correlation coefficient = 0,94]. There is a reverse correlation between the CDH1 mRNA expression level and the degree of histological differentiation of intestinal-type gastric adenocarcinoma (correlation coefficient γ = -0,44); there is a direct correlation between the CTNNB1 and CDH1 mRNA expression levels (only for the I clinical stage cases); there are a direct correlations between the E-cadherin and β-catenin expression levels, and also between the CTNNB1 mRNA expression level and the E-cadherin expression level (only for the I-II clinical stage cases). Conclusion. The data indicate that decrease of transcriptional activity of the CDH1 gene and E-cadherin expression level, and also increase of transcriptional activity of the CTNNB1 gene and β-catenin expression level in the cancer cells play a critical role in the process of progression of intestinal-type gastric adenocarcinoma.

Highlights

Молекулярно-генетические аномалии, которые лежат в основе аберрантной экспрессии Е-кадгерина и β-катенина в злокачественных опухолях, изучены недостаточно
In comparison with the normal stomach mucosa, the intestinal-type gastric adenocarcinoma differs by the reduced transcriptional activity of the CDH1 gene [Me of relative normalized ratio of mRNA expression level is 0.14 (0.03; 0.40)], which correlates with the low expression level of E-cadherin in cancer cells [Me is 27,59 CUOD (23,14; 37,19), Spearman’s correlation coefficient = 0,73], and by the heightened transcriptional activity of the CTNNB1 gene [Me of relative normalized ratio of mRNA expression level is 4.32 (2.11; 11.43)], which correlates with the high expression level of β-catenin in cancer cells [Me is 116.65 CUOD (110.34; 151.32), Spearman’s correlation coefficient = 0,94]
There is a reverse correlation between the CDH1 mRNA expression level and the degree of histological differentiation of intestinal-type gastric adenocarcinoma; there is a direct correlation between the CTNNB1 and CDH1 mRNA expression levels; there are a direct correlations between the E-cadherin and β-catenin expression levels, and between the CTNNB1 mRNA expression level and the E-cadherin expression level

Summary

Introduction

Молекулярно-генетические аномалии, которые лежат в основе аберрантной экспрессии Е-кадгерина и β-катенина в злокачественных опухолях, изучены недостаточно. Цель работы – сравнение уровней экспрессии мРНК генов CDH1 и CTNNB1 и экспрессии Е-кадгерина и β-катенина опухолевыми клетками аденокарциномы желудка кишечного типа (АКЖКТ). Аденокарцинома желудка кишечного типа в сравнении со слизистой оболочкой желудка обычного гистологического строения характеризуется сниженными показателями экспрессии мРНК гена CDH1 [Me = 0,14 (0,03; 0,40)], которые коррелируют с низким уровнем экспрессии опухолевыми клетками Е-кадгерина [Me = 27,59 УЕОП (23,14; 37,19)], коэффициент корреляции Спирмена = 0,73], а также повышенными показателями экспрессии мРНК гена CTNNB1 [Me = 4,32 (2,11; 11,43)], которые коррелируют с высоким уровнем экспрессии опухолевыми клетками β-катенина [Me = 116,65 УЕОП (110,34; 151,32), коэффициент корреляции Спирмена = 0,94]. Снижение транскрипционной активности гена CDH1 и уровня экспрессии Е-кадгерина, а также повышение транскрипционной активности гена CTNNB1 и уровня экспрессии β-катенина опухолевыми клетками АКЖКТ играют важную роль в прогрессии карциномы желудка

Objectives

Results

Conclusion