Integrated Analysis of lncRNA–miRNA–mRNA ceRNA Network in Order to Discover Potential Novel Biomarkers in Stomach Cancer

Abstract

Stomach cancer (SC) or gastric cancer (GC) is one of the most common gastrointestinal malignancies. Currently, some studies based on competing endogenous RNAs (ceRNA) network analysis have been assessed for this cancer. The construction and analysis of ceRNA network is a novel approach for identification of RNA‐based biomarkers in cancer studies. In the current study, our aim is to discover novel potential biomarker based on lncRNA, miRNA, and mRNA ceRNA network analysis. To do this, differentially expressed miRNAs (DEmiRNAs) between SC and normal samples have been collected from the DBDEMC website. Then, a list of lncRNAs regulating DEmiRNA is collected from the LncACTdb 3.0 database and the lncRNA–miRNA bipartite network has been constructed. Subsequently, target mRNAs of the DEmiRNAs have been collected from the miRTarBase website and a protein–protein interaction (PPI) network was constructed thanks to the STRING website. Afterwards, five gene modules were discovered from the PPI network. Thus, miRNA–mRNA bipartite network has been constructed for DEmiRNAs and modules' genes. Finally, lncRNA–miRNA–mRNA ceRNA network is constructed and analyzed. After analyzing the ceRNA network, it is observed that DANCR and MEG3 with degree three and XIST , MALAT1 , TTN‐AS1 , HOTAIR , HCAL , GAS5 with degree two, have the important role in the ceRNA network regulation. As well as, miR‐145‐5p, miR‐145‐3p, miR‐183‐5p, miR‐21‐5p are hub miRNAs in the ceRNA network and they are targeting more genes of the PPI modules' genes. Among the genes evaluated, miR‐96‐5p and miR‐183‐5p were the only candidates that exhibited significant differential expression between the normal and SC groups and showed a significant association with overall survival (OS) in patients with stomach cancer (log‐rank p < 0.05), underscoring their potential prognostic significance.