A novel three‑miRNA signature predicts survival in cholangiocarcinoma based on RNA‑Seq data

Abstract

Accumulating evidence illustrates that many microRNAs (miRNAs) are abnormally expressed in cholangiocarcinoma and play important roles in tumorigenesis, tumor progression and metastasis. These miRNAs may serve as prognostic biomarkers and potential therapeutic targets. The aim of the present study was to identify the differentially expressed miRNAs in cholangiocarcinoma tissues vs. normal tissues by analyzing high‑throughput data derived from The Cancer Genome Atlas (TCGA) database. Furthermore, we evaluated the prognostic performance of the differentially expressed miRNAs and developed a novel three‑miRNA signature which predicted survival in cholangiocarcinoma patients. According to the cut‑off criteria of P<0.01 and |log2FC|>1.0, a total of 100miRNAs (54upregulated and 46downregulated) were found to be differentially expressed and some of them were significantly associated with clinical features. Of the above 100miRNAs, we obtained three miRNAs (miR‑10b, miR‑22 and miR‑551b) which were markedly related to patient overall survival (OS). Subsequently, a novel three‑miRNA signature was established and validated to be effective to predict survival. The results demonstrated that the survival rate, as well as the survival time of patients were obviously enhanced in relation to a lower miRNA signature index. Univariate and multivariate Cox regression analyses revealed that the three‑miRNA signature was an independent prognostic factor in cholangiocarcinoma. The reliability of the three‑miRNA signature was validated by an independent cohort from Gene Expression Omnibus (GEO). Furthermore, the functional enrichment analysis emphasized that the target genes of the aforementioned miRNAs may be involved in a variety of pathways and processes associated with cancer. Finally, these three miRNAs were detected for verification of expression using RT‑qPCR, and miR‑551b was selected for the verification of biological functions in cholangiocarcinoma cells. The results revealed that overexpression of miR‑551b decreased cancer cell proliferation and promoted apoptosis. Collectively, the results of the present study indicated that a specific three‑miRNA signature could be considered as an alternative prognostic marker in cholangiocarcinoma.