作者
Răzvan Cristescu,Jeeyun Lee,Michael Nebozhyn,Kyoung‐Mee Kim,Jason C. Ting,Suei Nee Wong,Jiangang Liu,Yong Yue,Jian Wang,Kun Yu,Xiang S. Ye,In‐Gu Do,Shawn Liu,Lara Gong,Jake Fu,Jiamin Jin,Min Gew Choi,Tae Sung Sohn,Woo Jung Lee,Jae Moon Bae,Se Hoon Park,Insuk Sohn,Sin‐Ho Jung,Patrick Tan,Ronghua Chen,James S. Hardwick,Won Ki Kang,Mark Ayers,Hongyue Dai,Christoph Reinhard,Andrey Loboda,Amit Aggarwal
摘要
Gastric cancer, a leading cause of cancer-related deaths, is a heterogeneous disease. We aim to establish clinically relevant molecular subtypes that would encompass this heterogeneity and provide useful clinical information. We use gene expression data to describe four molecular subtypes linked to distinct patterns of molecular alterations, disease progression and prognosis. The mesenchymal-like type includes diffuse-subtype tumors with the worst prognosis, the tendency to occur at an earlier age and the highest recurrence frequency (63%) of the four subtypes. Microsatellite-unstable tumors are hyper-mutated intestinal-subtype tumors occurring in the antrum; these have the best overall prognosis and the lowest frequency of recurrence (22%) of the four subtypes. The tumor protein 53 (TP53)-active and TP53-inactive types include patients with intermediate prognosis and recurrence rates (with respect to the other two subtypes), with the TP53-active group showing better prognosis. We describe key molecular alterations in each of the four subtypes using targeted sequencing and genome-wide copy number microarrays. We validate these subtypes in independent cohorts in order to provide a consistent and unified framework for further clinical and preclinical translational research.