LncRNA and mRNA integration network reconstruction reveals novel key regulators in esophageal squamous-cell carcinoma

Abstract

Many experimental and computational studies have identified key protein coding genes in initiation and progression of esophageal squamous cell carcinoma (ESCC). However, the number of researches that tried to reveal the role of long non-coding RNAs (lncRNAs) in ESCC has been limited. LncRNAs are one of the important regulators of cancers which are transcribed dominantly in the genome and in various conditions. The main goal of this study was to use a systems biology approach to predict novel lncRNAs as well as protein coding genes associated with ESCC and assess their prognostic values. By using microarray expression data for mRNAs and lncRNAs from a large number of ESCC patients, we utilized "Weighted Gene Co-expression Network Analysis" (WGCNA) method to make a big coding-non-coding gene co-expression network, and discovered important functional modules. Gene set enrichment and pathway analysis revealed major biological processes and pathways involved in these modules. After selecting some protein coding genes involved in biological processes and pathways related to cancer, we used "LncTar", a computational tool to predict potential interactions between these genes and lncRNAs. By combining interaction results with Pearson correlations, we introduced some novel lncRNAs with putative key regulatory roles in the network. Survival analysis with Kaplan-Meier estimator and Log-rank test statistic confirmed that most of the introduced genes are associated with poor prognosis in ESCC. Overall, our study reveals novel protein coding genes and lncRNAs associated with ESCC, along with their predicted interactions. Based on the promising results of survival analysis, these genes can be used as good estimators of patients' survival, or even can be analyzed further as new potential signatures or targets for the therapy of ESCC disease.

Keywords: ESCC; Esophageal squamous cell carcinoma; Gene co-expression network; LncRNA and systems biology; Long non-coding RNA.