Weighted correlation network and differential expression analyses identify prognostic lncRNA-miRNA-mRNA-ceRNA regulatory network in esophageal squamous cell carcinoma
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Background Esophageal squamous cell carcinoma (ESCC) is one of the most common malignant tumours arose from the esophagus. ESCC is highly lethal due to the late onset of symptoms and therefore, there is an urgent need to deepen the molecular understanding of this disease and identify potential prognostic biomarkers to further guide ESCC treatment. As a type of non-coding RNAs, competing endogenous RNA (ceRNA) reveals a novel mechanism of interaction between RNAs in various cancers. However, the understanding of the ceRNA regulatory network in ESCC is still unclear. Methods In this study, RNA-seq and clinicopathological characteristics data of ESCC and normal esophageal tissues was obtained from TCGA and GTEx database, respectively. Differentially expressed genes (DEGs) between ESCC and normal esophagel tissues were identified by employing R package (edgeR). Functional enrichment analysis of these DEGs was performed through the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes-Gene Set Enrichment Analysis (KEGG-GSEA). Subsequently, multivariate cox and survival analysis were performed to evaluate these DEGs. Then the expression of these 9 DEGs was investigated through Q-PCR in normal esophageal epithelial and ESCC cells. Results Compared to normal tissues, a total of 794 mRNAs were up-regulated and 1118 mRNAs were down-regulated in ESCC. The results of GO analysis showed an enrichment of the up-regulated genes in leukocyte migration, humoral immune response, phagocytosis and complement activation. Meanwhile, the results of KEGG-GSEA analysis showed an enrichment of the up-regulated genes in cell cycle, p53 signaling pathway and extracellular matrix receptor interaction, while an enrichment of the down-regulated genes in vascular smooth muscle contraction, ribosome and oxidative phosphorylation. The survival analysis identified significant association of poor prognosis with five up-regulated genes and four down-regulated genes. Conclusion This study identified several differential expression genes with prognostic values, and these genes may provide new insights into the roles of ceRNA regulatory network in ESCC.