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

• Grant number: 12/15036-8
• Support Opportunities: Regular Research Grants
• Start date: November 01, 2012
• End date: October 31, 2014
• Field of knowledge: Biological Sciences - Genetics - Human and Medical Genetics
• Principal Investigator: Ana Elizabete Silva
• Grantee: Ana Elizabete Silva
• Host 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

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)

Scientific publications

(8)

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

TARGA CADAMURO, ALINE CRISTINA; TEIXEIRA ROSSI, ANA FLAVIA; BISELLI-PERICO, JOICE MATOS; PEREIRA, PATRICIA FUCUTA; BEDIN MASCARIN DO VALE, EDLA POLSINELLI; ACAYABA, RICARDO; MOREIRA LEITE, KTIA RAMOS; GOLONI-BERTOLLO, ENY MARIA; SILVA, ANA ELIZABETE. Effect of Helicobacter pylori Eradication on TLR2 and TLR4 Expression in Patients with Gastric Lesions. Mediators of Inflammation, 2015. (12/15036-8)

TEIXEIRA ROSSI, ANA FLAVIA; DUARTE, MARCIA CRISTINA; POLTRONIERI, AYLA BLANCO; VALSECHI, MARINA CURADO; JORGE, YVANA CRISTINA; NETO, DALISIO DE-SANTI; RAHAL, PAULA; OLIANI, SONIA MARIA; SILVA, ANA ELIZABETE. Deregulation of Annexin-A1 and Galectin-1 Expression in Precancerous Gastric Lesions: Intestinal Metaplasia and Gastric Ulcer. Mediators of Inflammation, 2014. (12/15036-8)

JORGE, YVANA CRISTINA; MATARUCO, MAYRA MIOTO; ARAUJO, LEANDRO PIRES; TEIXEIRA ROSSI, ANA FLAVIA; DE OLIVEIRA, JULIANA GARCIA; VALSECHI, MARINA CURADO; CAETANO, ALAOR; MIYAZAKI, KENJI; DE JESUS FAZZIO, CELIA SEBASTIANA; THOME, JORGE ALBERTO; et al. Expression of Annexin-A1 and Galectin-1 Anti-Inflammatory Proteins and mRNA in Chronic Gastritis and Gastric Cancer. Mediators of Inflammation, 2013. (12/15036-8)

POLTRONIERI-OLIVEIRA, AYLA BLANCO; MADEIRA, FERNANDA FERNANDEZ; SANTOS MARQUES NUNES, DENIS BRUNO; RODRIGUES, GABRIELA HELENA; LOPES, BEATRIZ CAMARGO; MANOEL-CAETANO, FERNANDA S.; BISELLI, JOICE MATOS; SILVA, ANA ELIZABETE. Polymorphisms of miR-196a2 (rs11614913) and miR-605 (rs2043556) confer susceptibility to gastric cancer. GENE REPORTS, v. 7, p. 154-163, JUN 2017. (12/15036-8)

TEIXEIRA ROSSI, ANA FLAVIA; DUARTE, MARCIA CRISTINA; POLTRONIERI, AYLA BLANCO; VALSECHI, MARINA CURADO; JORGE, YVANA CRISTINA; NETO, DALISIO DE-SANTI; RAHAL, PAULA; OLIANI, SONIA MARIA; SILVA, ANA ELIZABETE. Deregulation of Annexin-A1 and Galectin-1 Expression in Precancerous Gastric Lesions: Intestinal Metaplasia and Gastric Ulcer. Mediators of Inflammation, v. 2014, p. 11-pg., 2014-01-01. (12/15036-8)

TARGA CADAMURO, ALINE CRISTINA; TEIXEIRA ROSSI, ANA FLAVIA; BISELLI-PERICO, JOICE MATOS; PEREIRA, PATRICIA FUCUTA; BEDIN MASCARIN DO VALE, EDLA POLSINELLI; ACAYABA, RICARDO; MOREIRA LEITE, KTIA RAMOS; GOLONI-BERTOLLO, ENY MARIA; SILVA, ANA ELIZABETE. Effect of Helicobacter pylori Eradication on TLR2 and TLR4 Expression in Patients with Gastric Lesions. Mediators of Inflammation, v. 2015, p. 9-pg., 2015-01-01. (12/15036-8)

TEIXEIRA ROSSI, ANA FLAVIA; TARGA CADAMURO, ALINE CRISTINA; BISELLI-PERICO, JOICE MATOS; MOREIRA LEITE, KATIA RAMOS; SEVERINO, FABIO EDUARDO; REIS, PATRICIA P.; CORDEIRO, JOSE ANTONIO; SILVA, ANA ELIZABETE. Interaction between inflammatory mediators and miRNAs in Helicobacter pylori infection. Cellular Microbiology, v. 18, n. 10, p. 1444-1458, OCT 2016. (13/03625-1, 12/15036-8)

PROENCA, MARCELA ALCANTARA; DE OLIVEIRA, JULIANA GARCIA; TARGA CADAMURO, ALINE CRISTINA; SUCCI, MAYSA; NETINHO, JOAO GOMES; GOLONI-BERTOLO, ENY MARIA; PAVARINO, ERIKA CRISTINA; SILVA, ANA ELIZABETE. TLR2 and TLR4 polymorphisms influence mRNA and protein expression in colorectal cancer. WORLD JOURNAL OF GASTROENTEROLOGY, v. 21, n. 25, p. 7730-7741, JUL 7 2015. (12/15036-8)