Published online Oct 7, 2015. doi: 10.3748/wjg.v21.i37.10510
Peer-review started: April 28, 2015
First decision: June 8, 2015
Revised: June 19, 2015
Accepted: August 31, 2015
Article in press: August 31, 2015
Published online: October 7, 2015
Gastric cancer is in decline in most developed countries; however, it still accounts for a notable fraction of global mortality and morbidity related to cancer. High-throughput methods are rapidly changing our view and understanding of the molecular basis of gastric carcinogenesis. Today, it is widely accepted that the molecular complexity and heterogeneity, both inter- and intra-tumour, of gastric adenocarcinomas present significant obstacles in elucidating specific biomarkers for early detection of the disease. Although genome-wide sequencing and gene expression studies have revealed the intricate nature of the molecular changes that occur in tumour landscapes, the collected data and results are complex and sometimes contradictory. Several aberrant molecules have already been tested in clinical trials, although their diagnostic and prognostic utilities have not been confirmed thus far. The gold standard for the detection of sporadic gastric cancer is still the gastric endoscopy, which is considered invasive. In addition, genome-wide association studies have confirmed that genetic variations are important contributors to increased cancer risk and could participate in the initiation of malignant transformation. This hypothesis could in part explain the late onset of sporadic gastric cancers. The elaborate interplay of polymorphic low penetrance genes and lifestyle and environmental risk factors requires additional research to decipher their relative impacts on tumorigenesis. The purpose of this article is to present details of the molecular heterogeneity of sporadic gastric cancers at the DNA, RNA, and proteome levels and to discuss issues relevant to the translation of basic research data to clinically valuable tools. The focus of this work is the identification of relevant molecular changes that could be detected non-invasively.
Core tip: This article summarizes the evidence of heterogeneous gastric cancer molecular changes. Despite enormous research efforts, to date, none of the common DNA, RNA or protein aberrations have achieved the high sensitivities, specificities, and predictive values necessary for clinical utility. Complex interrogation schemes based on a systems medicine approach should be developed to determine effective therapeutic strategies and to identify molecular signatures that are specific for the early detection of gastric cancer and pre-malignant stomach lesions that could progress to malignant disease.