Respiratory Research Division, Department of Medicine, Education and Research Centre, Royal College of Surgeons in Ireland, Beaumont Hospital, Dublin 9, Ireland.
Immuno-Oncology Laboratory, Department of Paediatric Haematology/Oncology, Ospedale Pediatrico Bambino Gesù, Viale di S. Paolo 15, 00146, Rome, Italy.
Sci Rep. 2017 Jun 9;7(1):3140. doi: 10.1038/s41598-017-02694-0.
Malignant pleural mesothelioma (MPM) is an aggressive human cancer and miRNAs can play a key role for this disease. In order to broaden the knowledge in this field, the miRNA expression was investigated in a large series of MPM to discover new pathways helpful in diagnosis, prognosis and therapy. We employed nanoString nCounter system for miRNA profiling on 105 MPM samples and 10 healthy pleura. The analysis was followed by the validation of the most significantly deregulated miRNAs by RT-qPCR in an independent sample set. We identified 63 miRNAs deregulated in a statistically significant way. MiR-185, miR-197, and miR-299 were confirmed differentially expressed, after validation study. In addition, the results of the microarray analysis corroborated previous findings concerning miR-15b-5p, miR-126-3p, and miR-145-5p. Kaplan-Meier curves were used to explore the association between miRNA expression and overall survival (OS) and identified a 2-miRNA prognostic signature (Let-7c-5p and miR-151a-5p) related to hypoxia and energy metabolism respectively. In silico analyses with DIANA-microT-CDS highlighted 5 putative targets in common between two miRNAs. With the present work we showed that the pattern of miRNAs expression is highly deregulated in MPM and that a 2-miRNA signature can be a new useful tool for prognosis in MPM.
恶性胸膜间皮瘤（MPM）是一种侵袭性人类癌症，miRNA 可以在其中发挥关键作用。为了拓宽该领域的知识，我们对大量 MPM 样本进行了 miRNA 表达谱分析，以发现有助于诊断、预后和治疗的新途径。我们采用了 nanoString nCounter 系统对 105 个 MPM 样本和 10 个健康胸膜进行 miRNA 分析。对最显著失调的 miRNA 进行了 RT-qPCR 验证，验证样本集是独立的。我们鉴定了 63 个 miRNA 在统计学上显著失调。miR-185、miR-197 和 miR-299 经过验证研究后，被证实差异表达。此外，微阵列分析的结果证实了 miR-15b-5p、miR-126-3p 和 miR-145-5p 的先前发现。Kaplan-Meier 曲线用于探索 miRNA 表达与总生存期（OS）之间的关联，并确定了一个与缺氧和能量代谢相关的 2miRNA 预后特征（Let-7c-5p 和 miR-151a-5p）。DIANA-microT-CDS 的计算分析突出了两个 miRNA 之间的 5 个可能的共同靶标。通过本研究，我们表明 MPM 中 miRNA 表达模式高度失调，2miRNA 特征可以成为 MPM 预后的新有用工具。
