Expressão do receptor c-MET, seu ligante HGF e VEGF como marcadores tumorais no câncer gástrico dos tipos intestinal e difuso na população brasileira: estudo piloto para padronização da técnica de PCR quantitativo

Abstract

INTRODUCTION: Gastric cancer (GC) is the third leading cause of death among malignant tumors worldwide, causing approximately 900,000 deaths / year. Changes in oncogenes that encode tyrosine kinase receptors play an important role in the pathogenesis of GC. MET gene is a proto-oncogene wich encodes a tyrosine kinase receptor c-MET and it is required for embryonic development and tissue repair. The hepatocyte growth factor (HGF) is the only known ligand for c-Met receptor. The MET oncogene activation suppresses apoptosis andpromotes cell survival, proliferation, migration, differentiation and angiogenesis. Among the angiogenic factors, VEGF is the main regulator. Its biological function includes promoting mitosis of endothelial cells and stimulate their proliferation. The expression of these biomarkers in GC is relatively recent, population-based studies are needed to define theexpression pattern. OBJECTIVES: Technical standardization of qPCR to evaluate quantitatively, in paraffin tissue samples, the presence of gene expression of the MET, HGF and VEGF in GC diffuse and intestinal types. METHODS: 20 GC patients were studied, ten patients were GC of intestinal type (average age 72.1 years) and ten of the diffuse type(average age 50.1 years). In all patients, tissue samples were analyzed from the tumor and distant areas of the tumor tissue. The relative expression of the tumor markers c-Met, HGF and VEGF was performed by qPCR technique by comparing tumor and non-tumor samples and they were normalized with the constitutive gene GAPDH. RESULTS: For c-Met, 18/20 (90%) patients expressed the marker and 9/20 (45%) overexpressed this gene, in which three were intestinal GC patients and six were diffuse GC patients. For HGF, only 7/20 (35%) express this gene and it was overexpressed in 4/20 (20%) patients, in which two wereintestinal GC patients and two were diffuse GC patients. For VEGF, 20/20 (100%) patients expressed this marker and in 12/20 (60%) patients was observed overexpression, in which eight patients had diffuse GC and four had intestinal GC. CONCLUSIONS: The qPCR technique was standardized and suitable for expression analysis of the biomarkers c-Met, HGF and VEGF using paraffin embedded tissue samples. The continuation of this study, with more samples will be conducted to characterize the expression pattern of these biomarkers in the human CG in the Brazilian population.