Prognostic significance of deregulated microRNAs in uveal melanomas
Prognostic significance of deregulated microRNAs in uveal melanomas
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DOI：
10.3892/mmr.2019.9949
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发表时间：
2019-04-01
影响因子：
3.4
通讯作者：
Candido, Saverio
中科院分区：
文献类型：
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作者：
Falzone, Luca;Romano, Giovanni L.;Candido, Saverio
葡萄膜黑色素瘤（UM）是最常见的眼部原发性肿瘤。尽管开发了新的药物和筛查计划，但UM患者的预后仍然很差，并且没有有效的预后生物标志物能够识别高风险患者。因此，在本研究中，分析了TCGA UM（UVM）数据库中包含的microRNA（miRNA或miR）表达数据，以鉴定一组具有预后意义的miRNA，用作临床实践中的生物标志物。将患者分为2组，包括肿瘤分期（高级别与低级别）和状态（死亡与存活）;对这些组之间的miRNA表达进行差异分析。每组共鉴定出20种失调的miRNA。两组之间共有7种miRNAs。大多数常见的miRNA属于miR-506-514簇，已知参与UM的发展。评估20种选择的与肿瘤分期相关的miRNA的预后价值。12个miRNAs的失调（6个上调和6个下调）与UM患者的预后不良相关。随后，使用miRCancerdb和microRNA Data Integration Portal生物信息学工具来鉴定与20种miRNA相关的一组基因，并建立它们的相互作用水平。通过这种方法，确定了53个不同的负相关和正相关基因。最后，DIANA-mirPath预测途径和基因本体论富集分析进行了先前产生的基因列表，以建立其功能参与生物过程和分子途径。所有的miRNAs和基因都参与了通常在癌症中改变的分子途径，包括丝裂原活化蛋白激酶（MAPK）途径。总体而言，本研究的发现表明，与低级别疾病患者相比，miR-506-514簇、hsa-miR-592和hsa-miR-199 a-5 p的miRNA是高级别疾病患者中失调最严重的miRNA，并且与患者的总生存期（OS）严格相关。然而，需要进一步的体外和翻译方法来验证这些初步发现。
Uveal melanoma (UM) represents the most frequent primary tumor of the eye. Despite the development of new drugs and screening programs, the prognosis of patients with UM remains poor and no effective prognostic biomarkers are yet able to identify high-risk patients. Therefore, in the present study, microRNA (miRNA or miR) expression data, contained in the TCGA UM (UVM) database, were analyzed in order to identify a set of miRNAs with prognostic significance to be used as biomarkers in clinical practice. Patients were stratified into 2 groups, including tumor stage (high-grade vs. low-grade) and status (deceased vs. alive); differential analyses of miRNA expression among these groups were performed. A total of 20 deregulated miRNAs for each group were identified. In total 7 miRNAs were common between the groups. The majority of common miRNAs belonged to the miR-506-514 cluster, known to be involved in UM development. The prognostic value of the 20 selected miRNAs related to tumor stage was assessed. The deregulation of 12 miRNAs (6 upregulated and 6 downregulated) was associated with a worse prognosis of patients with UM. Subsequently, miRCancerdb and microRNA Data Integration Portal bioinformatics tools were used to identify a set of genes associated with the 20 miRNAs and to establish their interaction levels. By this approach, 53 different negatively and positively associated genes were identified. Finally, DIANA-mirPath prediction pathway and Gene Ontology enrichment analyses were performed on the lists of genes previously generated to establish their functional involvement in biological processes and molecular pathways. All the miRNAs and genes were involved in molecular pathways usually altered in cancer, including the mitogen-activated protein kinase (MAPK) pathway. Overall, the findings of the presents study demonstrated that the miRNAs of the miR-506-514 cluster, hsa-miR-592 and hsa-miR-199a-5p were the most deregulated miRNAs in patients with high-grade disease compared to those with low-grade disease and were strictly related to the overall survival (OS) of the patients. However, further in vitro and translational approaches are required to validate these preliminary findings.