Evaluation of gene and protein expression in inflammatory processes and neoplasms of the digestive tract: stomach and colorectal

Abstract

Recent studies have shown that chronic inflammation predisposes to different types of cancers, with the involvement of important components of the inflammatory process in carcinogenesis. In the digestive tract, stomach and colon both organs are exposed to various endogenous and exogenous factors related to lifestyle that may trigger the inflammatory process, such as infection by the bacterium H. pylori increases the risk for gastric cancer. The eradication of H. pylori is considered a first line treatment to revert to pre-neoplastic lesions and prevent tumor progression, but some patients have no effective response. Few studies have evaluated the occurrence of genetic changes before and after H. pylori eradication, which may help in understanding the major changes related to patient response to therapy in association with the genotypes of bacterial virulence. Colorectal cancer (CRC) also fits as a model of carcinogenesis associated with inflammation such as ulcerative colitis and infection by the bacterium Fusobacterium nucleatum. Often its development follows the adenoma-carcinoma sequence, and in most cases, the CCR arises as adenomatous polyps. Given the above, this project aims to evaluate the mRNA expression of genes that act in the host inflammatory response such as TLR2, TLR4, IL-8, TGF-², PAP, PAI-1, PLAT IFITM1 in patients with dyspepsia gastric before and after therapy for the eradication of H. pylori, with the technique of real-time qPCR; to investigate the protein expression of their genes by immunohistochemistry, and to investigate the virulent cagA genotypes of H. pylori and association with response to H. pylori eradication, but also with the pattern of gene and protein expression. Recently we completed a research on gene and protein expression of annexin-1 and Galectin-1, anti-inflammatory action in chronic gastritis and gastric cancer that showed high expression of mRNA and protein annexin-1 in gastritis and gastric cancer, but galectin-1 showed high expression only in gastric cancer. Therefore it is interesting to also investigate other precursor lesions that are part of the cascade of progression of stomach cancer. Therefore, we intend to evaluate mRNA expression of genes ANXA1 (annexin-1) and LGALS1 (galectin-1) and protein expression in samples of intestinal metaplasia, gastric ulcer and gastric mucosa normal by qPCR technique in real time and immuno- staining, respectively, and associated with the infection by H. pylori virulence genotypes cagA. Likewise in colorectal carcinoma and its precursor lesions adenoma, are also analyzed the levels of gene and protein expression of annexin-1 and galectin-1 and proliferation index by Ki-67 antigen and association with the abundance of the bacterium Fusobacterium nucleatum. Also in CCR intend to evaluate the levels of gene expression of receptors TLR2 and TLR4 pathogens that have functional polymorphisms such as -196 to -174 del TLR2 and TLR4 -1607 T / C to evaluate their possible influence as the carriers of the genotypes in the wild or polymorphic levels of expression of these genes and susceptibility to sporadic colorectal cancer. The results may reveal changes in the expression of important genes associated with inflammation, which may help in future strategies for more effective therapy of these lesions and prevention of malignant progression. (AU)