通过 WGCNA 共表达网络分析揭示结肠癌复发相关基因。

Colon cancer recurrence‑associated genes revealed by WGCNA co‑expression network analysis.

机构信息

Department of Integrative Oncology, Changhai Hospital of Traditional Chinese Medicine, Second Military Medical University, Shanghai 200433, P.R. China.

Department of Anesthesiology, 264 Hospital of The People's Liberation Army, Taiyuan, Shanxi 030001, P.R. China.

出版信息

Mol Med Rep. 2017 Nov;16(5):6499-6505. doi: 10.3892/mmr.2017.7412. Epub 2017 Aug 31.

Abstract

The present study aimed to identify the recurrence‑associated genes in colon cancer, which may provide theoretical evidence for the development of novel methods to prevent tumor recurrence. Colon cancer and matched normal samples microarray data (E‑GEOD‑39582) were downloaded from ArrayExpress. Genes with significant variation were identified, followed by the screening of differentially expressed genes (DEGs). Subsequently, the co‑expression network of DEGs was constructed using the weighted correlation network analysis (WGCNA) method, which was verified using the validation dataset. The significant modules associated with recurrence in the network were subsequently screened and verified in another independent dataset E‑GEOD‑33113. Function and pathway enrichment analyses were also conducted to determine the roles of selected genes. Survival analysis was performed to identify the association between these genes and survival. A total of 434 DEGs were identified in the colon samples, and stress‑associated endoplasmic reticulum protein family member 2 (SERP2) and long non‑coding RNA‑0219 (LINC0219) were determined to be the vital DEGs between all the three sub‑type groups with different clinical features. The brown module was identified to be the most significant module in the co‑expression network associated with the recurrence of colon cancer, which was verified in the E‑GEOD‑33113 dataset. Top 10 genes in the brown module, including EGF containing fibulin like extracellular matrix protein 2 (EFEMP2), fibrillin 1 (FBN1) and secreted protein acidic and cysteine rich (SPARC) were also associated with survival time of colon cancer patients. Further analysis revealed that the function of cell adhesion, biological adhesion, extracellular matrix (ECM) organization, pathways of ECM‑receptor interaction and focal adhesion were the significantly changed terms in colon cancer. In conclusion, SERP2, EFEMP2, FBN1, SPARC, and LINC0219 were revealed to be the recurrence‑associated molecular and prognostic indicators in colon cancer by WGCNA co‑expression network analysis.

摘要

本研究旨在鉴定结肠癌复发相关基因,为开发预防肿瘤复发的新方法提供理论依据。从 ArrayExpress 下载结肠癌和匹配正常样本微阵列数据(E-GEOD-39582)。鉴定具有显著差异的基因,然后筛选差异表达基因(DEGs)。随后,使用加权相关网络分析(WGCNA)方法构建 DEGs 的共表达网络,并使用验证数据集进行验证。随后在另一个独立数据集 E-GEOD-33113 中筛选和验证与网络中复发相关的显著模块。还进行了功能和通路富集分析,以确定所选基因的作用。进行生存分析以确定这些基因与生存之间的关联。在结肠样本中鉴定出 434 个 DEG,并且确定应激相关内质网蛋白家族成员 2(SERP2)和长非编码 RNA-0219(LINC0219)是具有不同临床特征的所有三个亚组类型之间的重要 DEG。在与结肠癌复发相关的共表达网络中,鉴定出棕色模块是最显著的模块,在 E-GEOD-33113 数据集得到验证。棕色模块中的前 10 个基因,包括富含表皮生长因子的纤维连接蛋白样细胞外基质蛋白 2(EFEMP2)、原纤维蛋白 1(FBN1)和富含半胱氨酸的分泌蛋白(SPARC),也与结肠癌患者的生存时间相关。进一步分析表明,细胞黏附、生物黏附、细胞外基质(ECM)组织、ECM-受体相互作用和黏着斑途径是结肠癌中显著改变的术语。总之,通过 WGCNA 共表达网络分析发现,SERP2、EFEMP2、FBN1、SPARC 和 LINC0219 是结肠癌复发相关的分子和预后指标。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1012/5865817/b826642b0150/mmr-16-05-6499-g02.jpg

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