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Evaluation of the expression of anti-inflammatory protein annexin-1 and gelectin-1 in gastric ulcer and intestinal metaplasia

Grant number: 11/11559-3
Support type:Scholarships in Brazil - Scientific Initiation
Effective date (Start): August 01, 2011
Effective date (End): July 31, 2012
Field of knowledge:Biological Sciences - Genetics - Human and Medical Genetics
Principal Investigator:Ana Elizabete Silva
Grantee:Ana Flávia Teixeira Rossi Freire
Home Institution: Instituto de Biociências, Letras e Ciências Exatas (IBILCE). Universidade Estadual Paulista (UNESP). Campus de São José do Rio Preto. São José do Rio Preto , SP, Brazil

Abstract

Gastric cancer remains the second leading cause of cancer-related death worldwide, despite the reduction in its incidence. The main risk factors consist of premalignant lesions of the gastric mucosa, such as chronic gastritis, metaplasia and dysplasia, often initiated by chronic inflammation caused by the bacterium Helicobacter pylori. Gastric ulcer, a chronic injury of the gastric mucosa, can also precede the process of stomach carcinogenesis. The progression of this cascade of injury is determined by multiple factors, including bacterial genotype, host genetic predisposition and exposure to other environmental factors as diet and smoking. Among the host genetic factors is the expression of genes involved in inflammatory response to infection by bacteria, such as encoders of anti-inflammatory proteins as annexin-1 and Galectin-1. Changes in the expression of these proteins have been associated with tumor progression suggesting a role in regulating cell proliferation, migration / invasion of epithelial cells. However in gastric carcinogenesis there are few studies with conflicting results, so the expression pattern of these genes and involvement in this type of cancer is unclear. In addition in precursor lesions such as metaplasia and ulcer such studies are practically absent. Recently we completed a research on gene and protein expression of annexin-1 and Galectin-1 in chronic gastritis and gastric cancer with interesting results, we observe both the mRNA and protein expression of annexin-1 higher in gastritis and gastric cancer, while galectin-1 showed high expression only in gastric cancer. So was observed altered expression of these genes in an initial injury and cancer, so it is interesting to also investigate other precursor lesions that are part of the cascade of progression of stomach cancer. Thus, considering the role of inflammation as a mediator of the carcinogenic process and that many transcriptional changes that alter the levels of gene expression occur in the early stages of cancer development and can be detected in precursor lesions, the objectives of this study are: (a) evaluate the quantitative mRNA expression of genes ANXA1 (annexin 1) and LGALS1 (galectin 1) involved in the inflammatory response in samples of intestinal metaplasia, gastric ulcer and normal gastric mucosa, by PCR in real time; (b) evaluate the expression of these proteins by immunohistochemistry in the same samples and check for compliance with the levels of mRNA expression, and (c) investigate the occurrence of infection by H. pylori and the cagA genotype as well as the occurrence of altered pattern of association between gene and protein expression and genotype with infection of the bacterium. The results should provide new knowledge about the expression pattern of anti-inflammatory protein ANXA1 and Gal-1 in gastric precancerous lesions and comparison with the results in chronic gastritis and gastric adenocarcinoma. This information may help in understanding the changes that occur in expression levels of these proteins in carcinogenesis of the stomach in association with the cagA bacterial virulence factor, further research may help to establish strategies for detecting risk groups with the establishment of diagnostic earlier and more effective therapies to combat inflammation.