Identification of prognostic miRNA biomarkers for esophageal cancer based on The Cancer Genome Atlas and Gene Expression Omnibus

MicroRNAs (miRNAs) in tumor and tumor-adjacent tissues can be effective diagnostic and prognostic markers to monitor tumor occurrence and progression. Despite improvements in the diagnosis and treatment of esophageal cancer (EC), the survival rate is <25%; consequently, more effective EC-specific prognostic biomarkers are urgently needed to design effective treatment regimens. In this study, we focused on identifying independent prognostic miRNA signatures in tumor and tumor-adjacent tissues in EC. We screened candidate miRNAs using a genome-wide miRNA transcriptome dataset from The Cancer Genome Atlas (TCGA) database that included 82 patients with esophageal adenocarcinoma (EADC) and 83 patients with esophageal squamous cell carcinoma (ESCC). We validated potential prognostic miRNA markers using a microarray profiling dataset that included information of 32 patients with EADC and 44 patients with ESCC from the Gene Expression Omnibus database. TCGA dataset was additionally used to identify differentially expressed mRNAs (DEMs) between the tumor and tumor-adjacent tissues. Univariate and multivariate Cox analyses were performed to detect the relationship between miRNAs and the overall survival of patients with EC. Kaplan–Meier method was applied to assess the survival differences between groups with differential miRNA expression. Lastly, functional enrichment analysis was conducted using miRWalk 2.0 online database for annotation. Although there was a considerable difference between the DEMs of EADC and ESCC, 73 DEMs were differentially expressed in both EADC and ESCC samples in TCGA dataset. Cox regression and Kaplan–Meier survival analyses showed that a higher expression of hsa-miR-186-5p and hsa-let-7d-5p was independently associated with a poor prognosis of EADC and ESCC, respectively. Furthermore, gene functional enrichment analysis revealed that the target genes of hsa-miR-186-5p and hsa-let-7d-5p participated in various cancer-related pathways, including the MAPK signaling pathway, proteoglycans in cancer, and AGE-RAGE signaling pathway. Our results revealed that hsa-miR-186-5p and hsa-let-7d-5p could be used as independent prognostic biomarkers for EADC and ESCC, respectively.