Downregulation of microRNA-374a predicts poor prognosis in human glioma
Downregulation of microRNA-374a predicts poor prognosis in human glioma
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DOI：
10.3892/etm.2019.7190
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发表时间：
2019-03-01
影响因子：
2.7
通讯作者：
Pan, Yawen
中科院分区：
文献类型：
--
作者：
Dong, Qiang;Yuan, Guoqiang;Pan, Yawen
某些微小RNA（miRNA/miR）可用作各种类型癌症的预后生物标志物。本研究的目的是鉴定不同级别胶质瘤中异常表达的miRNAs，并评价其在胶质瘤患者中的临床意义。差异表达的miRNAs从使用微阵列平台确定的六个胶质瘤组织（三个低级别和三个高级别胶质瘤）的表达谱中进行评估。逆转录-定量聚合酶链反应分析用于进一步验证候选miRNA在42例患者和5例健康对照组中的异常表达。预测miRNA靶基因，构建蛋白质-蛋白质相互作用网络，并利用基因本体论（GO）和京都基因与基因组百科全书（KEGG）途径对靶基因进行功能富集分析。Kaplan-Meier曲线和Log-rank分析以及多变量考克斯回归分析来评估候选miRNA与患者存活率的关联。通过比较低级别和高级别胶质瘤组织，共鉴定出15种差异表达的miRNAs，包括13种下调和2种上调的miRNAs。高级别胶质瘤的miR-374 a表达显著低于低级别胶质瘤（倍数变化，-4.43; P=0.027）。随着胶质瘤病理分级的升高，miR-374 a的表达水平逐渐降低。Pearson卡方检验用于确定miR-374 a表达与几个临床病理因素的关联。此外，miR-374 a的低表达被确定为独立的预后标志物，并且与总生存率显著相关（P=0.0213）。GO和KEGG通路分析显示，miR-374 a的靶基因可能参与了RNA聚合酶II启动子和mTOR信号通路的调控。通过PPI网络分析，确定了4个中心基因（CCND 1，SP1，CDK 4，CDK 6）。结论：miR-374 a可作为胶质瘤高危人群筛查和预后评估的生物标志物。
Certain microRNAs (miRNAs/miRs) may be used as prognostic biomarkers in various types of cancer. The purpose of the present study was to identify miRNAs that were abnormally expressed in glioma of different grades, and to evaluate their clinical implications in patients with glioma. The differentially expressed miRNAs were evaluated from the expression profiles of six glioma tissues (three low-grade and three high-grade gliomas) determined using a microarray platform. Reverse transcription-quantitative polymerase chain reaction analysis was used to further verify the aberrant expression of the candidate miRNA in a set of 42 patients and 5 healthy controls. The miRNA target genes were predicted and the protein-protein interaction network was generated; furthermore, functional enrichment analysis of the target genes in Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways was performed. Kaplan-Meier curves and Log-rank analysis, as well as multivariate Cox regression analysis were performed to assess the association of the candidate miRNA with patient survival. A total of 15 differentially expressed miRNAs, including 13 downregulated and 2 upregulated miRNAs, were identified by comparison of low-grade and high-grade glioma tissues. The miR-374a expression of high-grade gliomas was significantly lower than that of low-grade gliomas (fold change, -4.43; P=0.027). The expression levels of miR-374a gradually decreased with the increase of the pathological grade of glioma. Pearson's Chi-square test was used to determine the association of miR-374a expression with several clinicopathological factors. Furthermore, low expression of miR-374a was determined to be an independent prognostic marker and that it was significantly associated with overall survival (P=0.0213). GO and KEGG pathway analysis revealed that the target genes of miR-374a may be involved in the regulation of the RNA polymerase II promoter and mTOR signaling pathway. The four hub genes (CCND1, SP1, CDK4, CDK6) were also identified by PPI network analysis. In conclusion, the present study indicated that miR-374a may be used as a promising prognostic biomarker for the screening of high-risk populations and for the assessment of the prognosis of patients with glioma.