Identificación de biomarcadores sanguíneos para la detección de lesiones premalignas y el diagnóstico del cáncer gástrico

Abstract

Introduction: Gastric cancer is very common in Colombia where it is the leading cause of death due to can­cer. According to the Pelayo Corre, there is a cascade of stages from gastritis through atrophy, metaplasia and dysplasia to cancer. In the intermediate stages, it might be possible to detect and prevent the development of cancer, but there are no known markers in the blood other than pepsinogen to help to detect premalignant stages and diagnose cancer. Research is the key to discovery of new biomarkers. Objective: The aim of this work is to identify molecular markers (mRNA expression profiles) that distinguish patients who have premalignant conditions (atrophy, metaplasia) and gastric cancer from patients who only have gastritis. Methodology: Following an initial endoscopy, patients in each stage of the Pelayo cascade fasted and then provided a 2.5 ml blood sample which was analyzed for gene expression. All participating patients signed consent forms prior to tests. The blood was placed in a PAXgene RNA Blood tube, RNA was extracted from the blood and then analyzed. A microarray platform which identified changes in messenger RNA expression was used to differentiate each of the stages described. Results: Endoscopic findings for the eighty-nine patients included showed that 25 (28%) had advanced gastric cancer, 7 (7.8%) had early cancer, 27 (30.3%) had chronic antral gastritis, 15 (16.8%) had chronic pangastritis, three (3.3%) were suspected of having atrophic gastritis, six (6.7%) were suspected of having intestinal metaplasia, and two (2.2%) had peptic ulcers. Pathological reports showed 20 cases of intestinal adenocarcinoma (4 women), 11 cases diffuse cancer (7 women), 34 cases of chronic gastritis (22 women), one case of atrophy alone, 18 cases of intestinal metaplasia (13 women), four cases of low-grade dysplasia, and one case of high-grade dysplasia. The analysis of genetic expression found 48 genes which could be used for differentiation of patients with chronic gastritis from patients with gastric cancer. We also found 14 genes that could be used to differentiate patients with diffuse cancer from patients with intestinal type gastric cancer, and a group of 48 genes that could be used to differentiate patients with chronic gastritis from those with intestinal metaplasia. Conclusions: This is the first work anywhere in the world that has identified new biomarkers through the genetic expression of messenger RNA which differentiates the stages of the Pelayo Correa cascade and permits diagnosis of gastric cancer. It is likely that in the future they may be used as diagnostic and/or follow-up tests.