Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis

Xian-Guo Zhou; Xiao-Liang Huang; Si-Yuan Liang; Shao-Mei Tang; Si-Kao Wu; Tong-Tong Huang; Zeng-Nan Mo; Qiu-Yan Wang

doi:10.2147/OTT.S163891

Identifying miRNA and gene modules of colon cancer associated with pathological stage by weighted gene co-expression network analysis

Onco Targets Ther. 2018 May 15:11:2815-2830. doi: 10.2147/OTT.S163891. eCollection 2018.

Authors

Xian-Guo Zhou^#^{1

2}, Xiao-Liang Huang^#^{1

2}, Si-Yuan Liang^{1

2

3}, Shao-Mei Tang^{1

2}, Si-Kao Wu^{1

2}, Tong-Tong Huang^{1

2}, Zeng-Nan Mo^{1

2

4}, Qiu-Yan Wang^{1

2

5}

Affiliations

¹ Center for Genomic and Personalized Medicine, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
² Guangxi Key Laboratory for Genomic and Personalized Medicine, Guangxi Collaborative Innovation Center for Genomic and Personalized Medicine, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
³ Department of Colorectal Surgery, First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
⁴ Department of Urology and Nephrology, The First Affiliated Hospital of Guangxi, Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.
⁵ Guangxi Colleges and Universities Key Laboratory of Biological Molecular Medicine Research, Guangxi Medical University, Nanning, Guangxi Zhuang Autonomous Region, People's Republic of China.

^# Contributed equally.

Abstract

Introduction: Colorectal cancer (CRC) is the fourth most common cause of cancer-related mortality worldwide. The tumor, node, metastasis (TNM) stage remains the standard for CRC prognostication. Identification of meaningful microRNA (miRNA) and gene modules or representative biomarkers related to the pathological stage of colon cancer helps to predict prognosis and reveal the mechanisms behind cancer progression.

Materials and methods: We applied a systems biology approach by combining differential expression analysis and weighted gene co-expression network analysis (WGCNA) to detect the pathological stage-related miRNA and gene modules and construct a miRNA-gene network. The Cancer Genome Atlas (TCGA) colon adenocarcinoma (CAC) RNA-sequencing data and miRNA-sequencing data were subjected to WGCNA analysis, and the GSE29623, GSE35602 and GSE39396 were utilized to validate and characterize the results of WGCNA.

Results: Two gene modules (Gmagenta and Ggreen) and one miRNA module were associated with the pathological stage. Six hub genes (COL1A2, THBS2, BGN, COL1A1, TAGLN and DACT3) were related to prognosis and validated to be associated with the pathological stage. Five hub miRNAs were identified to be related to prognosis (hsa-miR-125b-5p, hsa-miR-145-5p, hsa-let-7c-5p, hsa-miR-218-5p and hsa-miR-125b-2-3p). A total of 18 hub genes and seven hub miRNAs were predominantly expressed in tumor stroma. Proteoglycans in cancer, focal adhesion, extracellular matrix (ECM)-receptor interaction and so on were common pathways of the three modules. Hsa-let-7c-5p was located at the core of miRNA-gene network.

Conclusion: These findings help to advance the understanding of tumor stroma in the progression of CAC and provide prognostic biomarkers as well as therapeutic targets.

Keywords: colon adenocarcinoma; differentially expressed genes; differentially expressed miRNA; tumor stroma; weighted gene co-expression network analysis.