Department of Radiotherapy & Oncology, The Second Affiliated Hospital of Soochow University, Suzhou, China.
Institute of Radiotherapy & Oncology, Soochow University, Suzhou, China.
Cancer Med. 2019 Oct;8(13):5995-6009. doi: 10.1002/cam4.2520. Epub 2019 Aug 25.
A series of studies have investigated the vital role of microRNA-181 (miR-181) in the initiation and development of colorectal cancer (CRC), and demonstrated that it might be associated with the prognosis of CRC. However, inconsistent findings have hindered its clinical application.
A comprehensive meta-analysis and an integrative bioinformatics analysis were carried out for concluding current available evidence, clarifying the preliminary prognostic value and unfolding the underlying biological function of miR-181 in CRC patients.
The findings revealed that elevated expression levels of miR-181 were associated with significantly poorer overall survival rates (HR = 1.75, 95% CI: 1.26-2.43, P < .05). Meanwhile, the target genes of miR-181 were identified and enriched into several important gene ontology (GO) categories and signaling pathways including miRNAs in cancer, pathways in cancer, proteoglycans in cancer, colorectal cancer, FoxO signaling pathway, PI3K-Akt signaling pathway, VEGF signaling pathway, HIF-1 signaling pathway, mTOR signaling pathway, and cAMP signaling pathway, which were confirmed highly involved in the initiation and progression of CRC. In addition, the protein-protein interaction (PPI) networks were set up by miR-181 targets to screen hub nodes and significant modules, which were also considerably associated with the molecular pathogenesis of CRC.
The present study demonstrated that miR-181 could be a promising biomarker with predictive value for prognosis for CRC patients. However, future studies comprising large cohorts from multicenter are warranted to further investigate the biomarker value of miR-181.
一系列研究已经探讨了 microRNA-181(miR-181)在结直肠癌(CRC)的发生和发展中的重要作用,并表明它可能与 CRC 的预后有关。然而,不一致的研究结果阻碍了其临床应用。
进行了全面的荟萃分析和综合的生物信息学分析,以总结当前可用的证据,阐明 miR-181 在 CRC 患者中的初步预后价值,并揭示其潜在的生物学功能。
研究结果表明,miR-181 的高表达水平与总生存率显著降低相关(HR=1.75,95%CI:1.26-2.43,P<0.05)。同时,鉴定了 miR-181 的靶基因,并将其富集到几个重要的基因本体(GO)类别和信号通路中,包括癌症中的 miRNAs、癌症信号通路、癌症中的蛋白聚糖、结直肠癌、FoxO 信号通路、PI3K-Akt 信号通路、VEGF 信号通路、HIF-1 信号通路、mTOR 信号通路和 cAMP 信号通路,这些通路被证实与 CRC 的发生和进展高度相关。此外,通过 miR-181 靶基因构建了蛋白质-蛋白质相互作用(PPI)网络,以筛选关键节点和显著模块,这些模块也与 CRC 的分子发病机制密切相关。
本研究表明,miR-181 可能是一种有前途的、具有预测价值的 CRC 患者预后的生物标志物。然而,需要包含来自多个中心的大样本队列的进一步研究来进一步探讨 miR-181 的生物标志物价值。