Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Department of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. ChinaDepartment of Hepatobiliary Surgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi 710061, P.R. China.
Oncol Rep. 2018 Sep;40(3):1422-1434. doi: 10.3892/or.2018.6534. Epub 2018 Jun 27.
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 100 miRNAs (54 upregulated and 46 downregulated) were found to be differentially expressed and some of them were significantly associated with clinical features. Of the above 100 miRNAs, 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.
越来越多的证据表明，许多 microRNAs（miRNAs）在胆管癌中异常表达，并在肿瘤发生、肿瘤进展和转移中发挥重要作用。这些 miRNA 可能作为预后生物标志物和潜在的治疗靶点。本研究旨在通过分析来自癌症基因组图谱（TCGA）数据库的高通量数据，鉴定胆管癌组织与正常组织中差异表达的 miRNAs。此外，我们评估了差异表达 miRNA 的预后性能，并开发了一种新的三 miRNA 特征，用于预测胆管癌患者的生存情况。根据 P<0.01 和 |log2FC|>1.0 的截止标准，共发现 100 个 miRNA（54 个上调和 46 个下调）差异表达，其中一些与临床特征显著相关。在上述 100 个 miRNA 中，我们获得了与患者总生存期（OS）显著相关的三个 miRNA（miR-10b、miR-22 和 miR-551b）。随后，建立并验证了一个新的三 miRNA 特征，以有效预测生存。结果表明，miRNA 特征指数越低，患者的生存率和生存时间明显提高。单因素和多因素 Cox 回归分析表明，三 miRNA 特征是胆管癌的独立预后因素。来自基因表达综合数据库（GEO）的独立队列验证了三 miRNA 特征的可靠性。此外，功能富集分析强调，上述 miRNA 的靶基因可能参与与癌症相关的多种途径和过程。最后，使用 RT-qPCR 验证了这三个 miRNA 的表达，选择 miR-551b 验证其在胆管癌细胞中的生物学功能。结果表明，miR-551b 的过表达降低了癌细胞的增殖并促进了细胞凋亡。综上所述，本研究结果表明，特定的三 miRNA 特征可作为胆管癌的替代预后标志物。
