Jiang Bitao, Sun Qingsen, Tong Yao, Wang Yuzhuo, Ma Haifen, Xia Xuefei, Zhou Yu, Zhang Xingguo, Gao Feng, Shu Peng
Department of Hematology and Oncology, Beilun People's Hospital, Ningbo.
Department of Gastrointestinal Hernia Surgery, CangZhou People's Hospital, CangZhou.
Medicine (Baltimore). 2019 Jul;98(27):e16273. doi: 10.1097/MD.0000000000016273.
Although the outcome of patients with gastric cancer (GC) has improved significantly with the recent implementation of annual screening programs. Reliable prognostic biomarkers are still needed due to the disease heterogeneity. Increasing pieces of evidence revealed an association between immune signature and GC prognosis. Thus, we aim to build an immune-related signature that can estimate prognosis for GC.
For identification of a prognostic immune-related gene signature (IRGS), gene expression profiles and clinical information of patients with GC were collected from 3 public cohorts, divided into training cohort (n = 300) and 2 independent validation cohorts (n = 277 and 433 respectively).
Within 1811 immune genes, a prognostic IRGS consisting of 16 unique genes was constructed which was significantly associated with survival (hazard ratio [HR], 3.9 [2.78-5.47]; P < 1.0 × 10). In the validation cohorts, the IRGS significantly stratified patients into high- vs low-risk groups in terms of prognosis across (HR, 1.84 [1.47-2.30]; P = 6.59 × 10) and within subpopulations with stage I&II disease (HR, 1.96 [1.34-2.89]; P = 4.73 × 10) and was prognostic in univariate and multivariate analyses. Several biological processes, including TGF-β and EMT signaling pathways, were enriched in the high-risk group. T cells CD4 memory resting and Macrophage M2 were significantly higher in the high-risk risk group compared with the low-risk group.
In short, we developed a prognostic IRGS for estimating prognosis in GC, including stage I&II disease, providing new insights into the identification of patients with GC with a high risk of mortality.
尽管随着近期年度筛查项目的实施,胃癌(GC)患者的预后有了显著改善。但由于疾病的异质性,仍需要可靠的预后生物标志物。越来越多的证据表明免疫特征与GC预后之间存在关联。因此,我们旨在构建一个能够评估GC预后的免疫相关特征。
为了鉴定预后免疫相关基因特征(IRGS),从3个公共队列中收集了GC患者的基因表达谱和临床信息,分为训练队列(n = 300)和2个独立验证队列(分别为n = 277和433)。
在1811个免疫基因中,构建了一个由16个独特基因组成的预后IRGS,其与生存显著相关(风险比[HR],3.9[2.78 - 5.47];P < 1.0×10)。在验证队列中,IRGS在总体(HR,1.84[1.47 - 2.30];P = 6.59×10)以及I&II期疾病亚组(HR,1.96[1.34 - 2.89];P = 4.73×10)中,根据预后将患者显著分层为高风险组和低风险组,并且在单变量和多变量分析中具有预后价值。包括TGF-β和EMT信号通路在内的几个生物学过程在高风险组中富集。高风险组中T细胞CD4记忆静止细胞和巨噬细胞M2显著高于低风险组。
简而言之,我们开发了一种用于评估GC(包括I&II期疾病)预后的预后IRGS,为识别具有高死亡风险的GC患者提供了新的见解。