其次,研究团队进一步分析这些分子分型与临床表型的相关性,他们主要观察了三种趋势:(1)MSS/EMT亚型显著地在年轻群体中出现;(2)MSI亚型以75%的概率出现在胃窦中,60%以上的本亚型具有肠亚型,50%以上的患者在早期会被诊断出来;(3)相对于其它群体来说,EBV感染频率在MSS/TP53+群体中更高。另外,他们还对这四种亚型进行了生存分析,观察总生存数的大量差异,发现MSI亚型预后最好,其次是MSS/TP53+和MSS/TP53-,MSS/EMT表现出了最差的预后。最后他们利用来自于亚洲肿瘤研究人群(ACRG)和SMC-2人群的临床数据分析了不同亚型的复发模式,MSS/EMT群体复发率高于MSI群体(63% VS 23%)。除此之外,他们观察到复发的第一位点与以下亚型相关:(1)受试者在MSS/EMT亚型中的腹膜种植率(64%)高于其它三种之和(23%);(2)MSI(23%)和MSS/TP53-(21%)的肝转移率高于MSS/EMT(4.6%)和MSS/TP53+(8%),这进一步加强了此种分类的临床相关性。
Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes
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.