Co-expression network analysis identified CDH11 in association with progression and prognosis in gastric cancer.
Co-expression network analysis identified CDH11 in association with progression and prognosis in gastric cancer.
复制标题
DOI：
10.2147/ott.s176511
复制
发表时间：
2018
影响因子：
4
通讯作者：
Zhao Q
中科院分区：
文献类型：
--
作者：
Chen PF;Wang F;Nie JY;Feng JR;Liu J;Zhou R;Wang HL;Zhao Q
胃癌是世界上最常见的癌症之一，其发病机制与复杂的基因相互作用网络有关。本研究的目的是寻找与胃癌进展和预后相关的中枢基因，并阐明其潜在机制。利用基因表达综合数据库（GEO）中的胃癌患者的临床数据和微阵列数据集进行加权基因共表达网络分析（WGCNA），以鉴定与胃癌TNM分期相关的重要基因模块和枢纽基因。利用显著模块基因进行功能富集分析和蛋白质-蛋白质相互作用网络分析。我们将共表达网络和蛋白质-蛋白质相互作用（PPI）网络中的共同枢纽基因视为“真实的”枢纽基因进行进一步分析。Hub基因在另一个独立数据集和癌症基因组图谱（TCGA）数据集中进行了验证。在显著紫色模块（R2=0.35）中，共鉴定出12个网络枢纽基因，其中6个也是模块基因的PPI网络中的枢纽节点。功能注释显示，紫色模块中的基因主要集中在系统发育、生物粘附、细胞外结构组织和代谢过程等生物学过程。在验证方面，CDH 11与TNM分期的相关性高于其他枢纽基因，并且基于GO功能富集分析与生物粘附强相关。基因表达谱交互分析（GEPIA）结果显示，CDH 11表达与胃癌分期呈正相关（P<0.0001）。在测试集和Oncomine数据集中，CDH 11在GC组织中高表达（P<0.0001）。生存分析表明，具有高CDH 11表达的样品显示不良预后。考克斯回归分析显示CDH 11表达是胃癌预后的独立预测因子（HR=1.482，95%CI：1.015-2.164）。此外，基因集富集分析（GSEA）表明，多种肿瘤相关途径，特别是粘着斑，在CDH 11高表达的样品中富集。CDH 11被鉴定并证实与GC的进展和预后相关，可能通过调节生物粘附和粘着斑相关途径。
Gastric cancer (GC) is one of the most common cancers worldwide, and its pathogenesis is related to a complex network of gene interactions. The aims of our study were to find hub genes associated with the progression and prognosis of GC and illustrate the underlying mechanisms. Weighted gene co-expression network analysis (WGCNA) was conducted using the microarray dataset and clinical data of GC patients from Gene Expression Omnibus (GEO) database to identify significant gene modules and hub genes associated with TNM stage in GC. Functional enrichment analysis and protein–protein interaction network analysis were performed using the significant module genes. We regarded the common hub genes in the co-expression network and protein–protein interaction (PPI) network as “real” hub genes for further analysis. Hub gene was validated in another independent dataset and The Cancer Genome Atlas (TCGA) dataset. In the significant purple module (R2=0.35), a total of 12 network hub genes were identified, among which six were also hub nodes in the PPI network of the module genes. Functional annotation revealed that the genes in the purple module focused on the biological processes of system development, biological adhesion, extracellular structure organization and metabolic process. In terms of validation, CDH11 had a higher correlation with the TNM stage than other hub genes and was strongly correlated with biological adhesion based on GO functional enrichment analysis. Data obtained from the Gene Expression Profiling Interactive Analysis (GEPIA) showed that CDH11 expression had a strong positive correlation with GC stages (P<0.0001). In the testing set and Oncomine dataset, CDH11 was highly expressed in GC tissues (P<0.0001). Survival analysis indicated that samples with a high CDH11 expression showed a poor prognosis. Cox regression analysis demonstrated an independent predictor of CDH11 expression in GC prognosis (HR=1.482, 95% CI: 1.015–2.164). Furthermore, gene set enrichment analysis (GSEA) demonstrated that multiple tumor-related pathways, especially focal adhesion, were enriched in CDH11 highly expressed samples. CDH11 was identified and validated in association with progression and prognosis in GC, probably by regulating biological adhesion and focal adhesion-related pathways.