Lin Xiandong, Zhao Yongzhong, Song Won-Min, Zhang Bin
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, NY 10029, USA ; Fujian Provincial Key Laboratory of Translational Cancer Medicine, Fujian Provincial Cancer Hospital, No. 420 Fuma Road, Jinan District, Fuzhou, Fujian 350014, PR China.
Department of Genetics and Genomic Sciences, Icahn Institute of Genomics and Multiscale Biology, Icahn School of Medicine at Mount Sinai, 1470 Madison Avenue, NY 10029, USA.
Comput Struct Biotechnol J. 2015 Aug 13;13:448-58. doi: 10.1016/j.csbj.2015.08.001. eCollection 2015.
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.
胃癌是一种高度异质性疾病,是癌症死亡的第二大主要原因,也是全球第四大常见癌症,东亚地区每年的病例数占全球一半以上。除了TNM分期外,胃癌临床还有两种公认的分类系统,即Lauren分类系统(将胃腺癌细分为肠型和弥漫型)以及世界卫生组织的另一种分类系统(将胃癌分为乳头状癌、管状癌、黏液性(胶样)癌和低黏附性癌)。这两种分类系统都有助于更好地理解胃癌的组织发生和生物学特性,但由于胃癌的分子异质性,它们在指导患者治疗方面的临床效用有限。前所未有的全基因组规模数据一直在推动和促进分子亚型分类方法的发展。在此,我们整理并比较了已发表的胃癌基因表达谱特征。我们基于体细胞突变、染色体不稳定、EB病毒感染和DNA甲基化的额外数据,总结了胃癌最近的综合基因组特征。我们确定了这些特征中的共识模式,并确定了潜在的分子途径和生物学功能。胃腺癌分子亚型分类的确定以及用于临床应用(如临床干预预测)的综合基因组学方法的开发,已成为胃癌个性化医疗的一个重要阶段。