Identificação de painel e perfil de expressão de genes regulados pelo oncogene myc em câncer gástrico

Abstract

Gastric cancer is the fourth most frequent neoplasm in the world. It causes more than 14,000 deaths per year in Brazil. Most gastric cancer research focuses on countries with high incidence rates, such as Japan. As the gastric cancer neoplasia is characterized by several factors, it is increasingly necessary to improve the management of gastric cancer in Brazil with the help of additional studies and public policies. The relative survival of individuals affected by gastric neoplasia is five years, which is actually considered low for both developed and developing countries. This poor prognosis is mainly due to late diagnosis leading to few treatment possibilities. Therefore, this work aims to investigate the genes regulated by the MYC oncogene to establish patterns of gene expression that guide tools for diagnosis and prognosis of gastric neoplasia. We used a cell line established from patients with gastric cancer of the metastatic type for, through MYC gene silencing, Next Generation Sequencing and quantitative Real-Time PCR (qRT-PCR) arrangements, to screen a panel of important genes regulated by MYC and their gene expression profiles. We selected three genes regulated by the MYC oncogene significantly

correlated to the stage of distant metastasis of gastric cancer from the panel of 150 down- regulated genes: UXT, MTA2, and CIAPIN1. We found all three genes strongly associated with

the more advanced stages of this cancer (P <0.0001). However, only UXT and CIAPIN1 were able to detect distant metastases in patients with early disease (P <0.0001) with high sensitivity (92.3% for UXT and 93.3% for CIAPIN1) and specificity (90.7% for UXT and 96.2% for CIAPIN1). In addition, the high expression of UXT and CIAPIN1 was significantly associated with a low overall survival of patients diagnosed with gastric cancer (P <0.0001). The study concludes that the MYC oncogene regulates thousands of genes in gastric carcinogenesis and some of these genes are associated with advanced stages of cancer, such as in individuals with distant metastases. Thus, such marker genes can be used to guide the prognosis and treatment of patients with gastric cancer.