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Authors Zhou X, Huang X, Liang S, Tang S, Wu S, Huang T, Mo Z, Wang Q
Received 27 January 2018
Accepted for publication 23 March 2018
Published 15 May 2018 Volume 2018:11 Pages 2815—2830
DOI https://doi.org/10.2147/OTT.S163891
Checked for plagiarism Yes
Review by Single-blind
Peer reviewers approved by Dr Cristina Weinberg
Peer reviewer comments 2
Editor who approved publication: Dr Carlos Vigil Gonzales
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, weighted gene co-expression network analysis,
differentially expressed genes, differentially expressed miRNA, tumor stroma