Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes
Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes
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DOI：
10.1038/nm.3850
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发表时间：
2015-05-01
期刊：
影响因子：
82.9
通讯作者：
Aggarwal, Amit
中科院分区：
文献类型：
--
作者：
Cristescu, Razvan;Lee, Jeeyun;Aggarwal, Amit
胃癌是一种异质性疾病，是癌症相关死亡的主要原因。我们的目标是建立临床相关的分子亚型，将包括这种异质性，并提供有用的临床信息。我们使用基因表达数据来描述与分子改变、疾病进展和预后的不同模式相关的四种分子亚型。间质样型包括弥漫型肿瘤，其预后最差，倾向于发生在较早的年龄，并且是四种亚型中复发频率最高的（63%）。微卫星不稳定肿瘤是发生在胃窦的高度突变的胃窦亚型肿瘤;在四种亚型中，它们具有最好的总体预后和最低的复发频率（22%）。肿瘤蛋白53（TP 53）-活性和TP 53-非活性类型包括具有中等预后和复发率（相对于其他两种亚型）的患者，其中TP 53-活性组显示出更好的预后。我们使用靶向测序和全基因组拷贝数微阵列描述了四种亚型中每一种的关键分子改变。我们在独立的队列中验证这些亚型，以便为进一步的临床和临床前转化研究提供一致和统一的框架。
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.