J Cancer 2020; 11(2):520-532. doi:10.7150/jca.29038

Research Paper

Translation of gastric disease progression at gene level expression

Stephanie Euridice Morales-Guerrero1, Claudia Ivette Rivas-Ortiz1, Sergio Ponce de León-Rosales2, Armando Gamboa-Domínguez2, Claudia Rangel-Escareño3, Luis Federico Uscanga-Domínguez2, Germán Rubén Aguilar-Gutiérrez4, David Kershenobich-Stalnikowitz2, Gonzalo Castillo-Rojas1✉, Yolanda López-Vidal1✉

1. Programa de Inmunología Molecular Microbiana, Departamento de Microbiología y Parasitología, Facultad de Medicina, Universidad Nacional Autónoma de México (UNAM), Ciudad de México, México
2. Dirección de Enseñanza, Departamentos de Gastroenterología, Patología y Dirección General. Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán (INCMNSZ), Ciudad de México, México
3. Departamento de Genómica Computacional, Instituto Nacional de Medicina Genómica (INMEGEN), Ciudad de México, México
4. Centro de Investigación Sobre Enfermedades Infecciosas (CISEI), Instituto Nacional de Salud Pública (INSP), Cuernavaca, Morelos, México

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Citation:
Morales-Guerrero SE, Rivas-Ortiz CI, Ponce de León-Rosales S, Gamboa-Domínguez A, Rangel-Escareño C, Uscanga-Domínguez LF, Aguilar-Gutiérrez GR, Kershenobich-Stalnikowitz D, Castillo-Rojas G, López-Vidal Y. Translation of gastric disease progression at gene level expression. J Cancer 2020; 11(2):520-532. doi:10.7150/jca.29038. Available from http://www.jcancer.org/v11p0520.htm

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Abstract

Helicobacter pylori is associated with the development of several lesions in the human stomach. This chronic infection produces gastritis, which can progress to intestinal metaplasia and gastric cancer. To date, there is very little information regarding gene-expression in the different phases of progression caused by chronic H. pylori infection. In this study, we performed a genome-wide gene-expression analysis in gastric biopsies of patients chronically infected with H. pylori, using the potential of high-throughput technologies that have not been fully exploited in this area. Here we illustrate the potential correlation of H. pylori infection with the gene expression changes in follicular gastritis, chronic gastritis and intestinal metaplasia. We also suggest its potential as biomarkers of each condition. An exploratory set of 21 biopsies from patients with follicular gastritis, chronic gastritis, and intestinal metaplasia were analyzed by gene-expression microarrays in order to identify the biological processes altered in each lesion. The microarray data was corroborated by real-time PCR, while 79 Formalin-Fixed Paraffin-Embeded samples were analyzed by immunohistochemistry. Follicular gastritis exhibited significant enrichment in genes associated with glutamate signaling, while chronic gastritis showed a down-regulation in metallothionein 1 and 2 and in oxidative phosphorylation-related genes, which could be associated with the chronic infecton of H. pylori. Intestinal metaplasia exhibited an over-expression of gastrointestinal stem cell markers, such as LGR5 and PROM1, as well as messenger RNA and nucleic acid metabolism-related genes. The gene-expression patterns found in this study provide new comparative information about chronic gastritis, follicular gastritis and intestinal metaplasia that may play an important role in the development of gastric cancer.

Keywords: Helicobacter pylori, microarray, gene expression, chronic gastritis, follicular gastritis, and intestinal metaplasia.