Molecular Prognostic Factors in Gastric Cancer

Abstract

Gastric cancer represents a major health problem worldwide. Literature data have demonstrated that gastric tumors present a high molecular heterogeneity, responsible for the process of carcinogenesis and dissemination. By revealing the molecular subtype of the tumor, it is possible to assess its behavior, the outcome of the patient, and the treatment approach, according to its genetic and epigenetic proile. This chapter aims to highlight some of the many diferent genetic mutations, epigenetic alterations, as well as aberrant signaling pathways involved in the pathogenesis of stomach cancers, each of these molecular abnormalities acting in a speciic stage of the disease. Moreover, the manuscript describes the novel therapeutic agents that target some of these aberrant molecular signaling pathways. Unfortunately, only a few agents are currently part of the standard treatment of gastric cancer, while most of the others remain to prove their therapeutic eicacy in the seting of clinical trials. By discovering the diferent molecular subtypes of gastric cancer, as well as numerous classes of targeted molecular agents, in the future, we would be able to perform an individualized treatment, associated with maximum eiciency and less costs.Keywords: gastric cancer, molecular classiication, gene expressions-based prognostic scoring system, molecular biomarkers, molecular targeted treatment IntroductionDespite a decline in the incidence in past decades, gastric cancer remains a major health problem globally [1,2], being the ifth most common type of cancer worldwide, with almost one million new cases estimated to have occurred in 2012, according to Globocan [3]. Furthermore, stomach cancer represents the third leading cause of cancer death in both sexes worldwide (723,000 deaths) [3].© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.According to the World Health Organization classiication, the vast majority of gastric cancers are adenocarcinomas, divided into papillary, tubular, mucinous (colloid), and poorly cohesive carcinomas (including signet-ring cell carcinoma and other variants) [4]. Although it was proposed a long time ago (1965), the Lauren classiication is still widely used in clinical practice and subdivides gastric carcinomas into intestinal and difuse types, associated with diferent pathogenesis, ways of spreading, and outcome [5]. Unfortunately, these two classiication systems have litle clinical impact, making the development of classiiers that can deine prognosis and guide patient's treatment as an urgent need.Literature data have demonstrated that the development of gastric cancer is associated in the majority of cases with infectious agents such as the Gram-negative spiral bacterium Helicobacter pylori (most often) [6] and Epstein-Barr virus (EBV) (about 9% o...