Hypomethylated gene NRP1 is co-expressed with PDGFRB and associated with poor overall survival in gastric cancer patients
Hypomethylated gene NRP1 is co-expressed with PDGFRB and associated with poor overall survival in gastric cancer patients
复制标题
低甲基化基因 NRP1 与 PDGFRB 共表达，与胃癌患者总生存率较差相关
DOI：
10.1016/j.biopha.2019.01.023
复制
发表时间：
2019-03-01
影响因子：
7.5
通讯作者：
She, Junjun
中科院分区：
文献类型：
--
作者：
Wang, Guanghui;Shi, Bin;She, Junjun
胃癌（Gastric cancer，GC）已成为日益严重的公共卫生问题。然而，目前仍缺乏及时有效的诊断和治疗方法，特别是在靶向治疗领域。越来越多的证据表明DNA甲基化在胃癌的发生、发展中起着重要作用。因此，本研究的目的是确定DNA甲基化为基础的预后生物标志物在GC。两个甲基化阵列数据集（GSE 25869和GSE 30601）和基于RNA-seq的基因谱数据集（TCGA-STAD）用于探索基于DNA甲基化的候选生物标志物。采用单因素考克斯回归分析筛选胃癌患者最有效的预后相关基因。采用加权基因相关网络分析（WGCNA）筛选共表达基因簇。因此，我们的数据证明，NRP 1是一个低甲基化/上调的基因在GC组织中，PDGFRB是强烈的共表达，他们都与患者的总生存率显着相关。更重要的是，NRP 1和PDGFRB的高表达水平与胃癌患者的恶性表型相关，包括Lauren组织学弥漫型和较高的组织学分级。携带NRP 1和PDGFRB高表达水平的患者的死亡风险比其他患者高近2倍。总之，低甲基化基因NRP 1及其共表达基因PDGFRB与肿瘤恶性表型显著相关，可能作为胃癌患者潜在的预后生物标志物。
Gastric cancer (GC) has been an increasingly serious problem in public health. However, there is still a lack of efficient approach to diagnosis and treatment in time, especially in the field of targeted therapy. Increasing evidences demonstrated that DNA methylation plays an essential role in tumorigenesis and progression of GC. Thus the present study aims to identify DNA methylation-based prognostic biomarkers in GC. Two methylation array datasets (GSE25869 and GSE30601) and RNA-seq based gene profiling dataset (TCGA-STAD) were employed for exploring candidate DNA methylation-based biomarkers. Univariate Cox regression analysis was used to select the most efficient prognostic genes in GC patients. Weighted gene correlation network analysis (WGCNA) was performed to screen the cluster of co-expressed genes. As a result, our data proved that NRP1 was a hypomethylated / upregulated gene in GC tissues, and PDGFRB was strongly co-expressed with it. Both of them were significantly associated with the overall survival of patients. More importantly, high expression levels of NRP1 and PDGFRB were associated with malignant phenotypes in GC patients, including Lauren histological diffuse type and higher histological grade. Patients carrying high expression level of NRP1 and PDGFRB had a nearly two-fold increased death risk than others. In summary, the hypomethylated gene, NRP1, and its co-expressed gene, PDGFRB, were significantly correlated with tumor malignant phenotypes, which might serve as potential prognostic biomarkers for GC patients.