Molecular classification and prediction in gastric cancer

Gastric cancer, a highly heterogeneous disease, is the second leading cause of cancer death and the fourth most common cancer globally, with East Asia accounting for more than half of cases annually. Alongside TNM staging, gastric cancer clinic has two well-recognized classification systems, the Lauren classification that subdivides gastric adenocarcinoma into intestinal and diffuse types and the alternative World Health Organization system that divides gastric cancer into papillary, tubular, mucinous (colloid), and poorly cohesive carcinomas. Both classification systems enable a better understanding of the histogenesis and the biology of gastric cancer yet have a limited clinical utility in guiding patient therapy due to the molecular heterogeneity of gastric cancer. Unprecedented whole-genome-scale data have been catalyzing and advancing the molecular subtyping approach. Here we cataloged and compared those published gene expression profiling signatures in gastric cancer. We summarized recent integrated genomic characterization of gastric cancer based on additional data of somatic mutation, chromosomal instability, EBV virus infection, and DNA methylation. We identified the consensus patterns across these signatures and identified the underlying molecular pathways and biological functions. The identification of molecular subtyping of gastric adenocarcinoma and the development of integrated genomics approaches for clinical applications such as prediction of clinical intervening emerge as an essential phase toward personalized medicine in treating gastric cancer.