Development of mesenchymal subtype gene signature for clinical application in gastric cancer.
Development of mesenchymal subtype gene signature for clinical application in gastric cancer.
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DOI：
10.18632/oncotarget.19985
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发表时间：
2017-09-12
期刊：
影响因子：
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通讯作者：
Kang WK
中科院分区：
文献类型：
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作者：
Lee J;Cristescu R;Kim KM;Kim K;Kim ST;Park SH;Kang WK
此前，在亚洲癌症研究小组（ACRG）项目中，我们在胃癌（GC）中定义了四种不同的分子亚型。间充质肿瘤（微卫星稳定，具有上皮-间充质过渡表型，MSS/EMT）在所有亚型中预后最差。为了建立预测间充质GC亚型的基因标记，我们使用NanoString方法对70个ACRG标本进行了基因表达谱分析。该基因标记在一组独立的前瞻性胃肿瘤辅助放化疗（ARTIST）试验中得到验证。研究了间充质亚型与生存率之间的关系。通过对70个ACRG样本进行跨平台一致性测试，获得了71个基因的MSS/EMT特征。在验证集中，基因标记预测73例患者中有20例（27%）患有间充质肿瘤。间充质亚型为弥漫性胃癌、低分化或印戒细胞癌，微卫星稳定。与非间充质肿瘤患者相比，间充质胃癌患者的估计生存风险比为2.262（95%可信区间，1.410 ~ 3.636；P=0.001）。当根据临床预后参数分析亚型时，生存差异仍然显著。这项研究表明，基于nanostring的间充质亚型71基因标记是胃癌患者预后的一个强有力的预测因子。
Previously, in the Asian Cancer Research Group (ACRG) project, we defined four distinct molecular subtypes in gastric cancer (GC). Mesenchymal (microsatellite stable with epithelial-to-mesenchymal transition phenotype, MSS/EMT) tumors showed the worst prognosis among all the subtypes. To develop a gene signature for predicting mesenchymal subtype GC, we conducted gene expression profiling using a NanoString assay in 70 ACRG specimens. The gene signature was validated in an independent set obtained from the prospective Adjuvant chemoRadioTherapy In Stomach Tumor (ARTIST) trial. The association between the mesenchymal subtype and survival was investigated. After cross-platform concordance test performed in 70 ACRG specimens, a 71-gene MSS/EMT signature was obtained. In the validation set, the gene signature predicted that 20 of 73 (27%) patients had mesenchymal tumors. Patients with mesenchymal subtype had diffuse GC, poorly-differentiated or signet ring cell carcinoma, and were microsatellite stable. The estimated hazard ratio for survival in patients with mesenchymal GC compared to those with non-mesenchymal tumors was 2.262 (95% confidence interval, 1.410 to 3.636; P=0.001). The survival difference remained significant when the subtypes were analyzed according to clinical prognostic parameters. This study suggested that the NanoString-based 71-gene signature for mesenchymal subtype is a strong predictor of the outcome in patients with GC.