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Comprehensive analysis of differential co-expression patterns reveal transcriptional dysregulation mechanism and identify novel prognostic lncRNAs in esophageal squamous cell carcinoma

Authors Li Z, Yao Q, Zhao S, Wang Y, Li Y, Wang Z

Received 21 February 2017

Accepted for publication 19 April 2017

Published 21 June 2017 Volume 2017:10 Pages 3095—3105

DOI https://doi.org/10.2147/OTT.S135312

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Narasimha Reddy Parine

Peer reviewer comments 2

Editor who approved publication: Dr Yao Dai

Zhen Li,1 Qianlan Yao,1 Songjian Zhao,1 Yin Wang,2,3 Yixue Li,1,4 Zhen Wang4

1School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, 2Shanghai Center for Bioinformation Technology, Shanghai Academy of Science and Technology, 3Collaborative Innovation Center for Genetics and Development, Fudan University, 4Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, People’s Republic of China

Abstract: Esophageal squamous cell carcinoma (ESCC) is one of the most common malignancies worldwide and occurs at a relatively high frequency in People’s Republic of China. However, the molecular mechanism underlying ESCC is still unclear. In this study, the mRNA and long non-coding RNA (lncRNA) expression profiles of ESCC were downloaded from the Gene Expression Omnibus database, and then differential co-expression analysis was used to reveal the altered co-expression relationship of gene pairs in ESCC tumors. A total of 3,709 mRNAs and 923 lncRNAs were differentially co-expressed between normal and tumor tissues, and we found that most of the gene pairs lost associations in the tumor tissues. The differential regulatory networking approach deciphered that transcriptional dysregulation was ubiquitous in ESCC, and most of the differentially regulated links were modulated by 37 TFs. Our study also found that two novel lncRNAs (ADAMTS9-AS1 and AP000696.2) might be essential in the development of ectoderm and epithelial cells, which could significantly stratify ESCC patients into high-risk and low-risk groups, and were much better than traditional clinical tumor markers. Further inspection of two risk groups showed that the changes in TF-target regulation in the high-risk patients were significantly higher than those in the low-risk patients. In addition, four signal transduction-related DCmRNAs (ERBB3, ENSA, KCNK7, MFSD5), which were differentially co-expressed with the two lncRNAs, might also have the predictive capacity. Our findings will enhance the understanding of ESCC transcriptional dysregulation from a view of cross-link of lncRNA and mRNA, and the two-lncRNA combination may serve as a novel prognostic biomarker for clinical applications of ESCC.

Keywords:
ESCC, differential co-expression analysis, differential regulation analysis, dysregulation, lncRNA, prognostic biomarker

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