Dong Qiang, Yuan Guoqiang, Liu Min, Xie Qiqi, Hu Jianhong, Wang Maolin, Liu Shangyu, Ma Xiaojun, Pan Yawen
Department of Neurosurgery, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Institute of Neurology, The Second Hospital of Lanzhou University, Lanzhou, Gansu 730030, P.R. China.
Exp Ther Med. 2019 Mar;17(3):2077-2084. doi: 10.3892/etm.2019.7190. Epub 2019 Jan 21.
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 () 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.
某些微小RNA（miRNA/miR）可作为多种类型癌症的预后生物标志物。本研究的目的是鉴定在不同级别胶质瘤中异常表达的miRNA，并评估其在胶质瘤患者中的临床意义。通过使用微阵列平台测定的六个胶质瘤组织（三个低级别和三个高级别胶质瘤）的表达谱来评估差异表达的miRNA。采用逆转录-定量聚合酶链反应分析进一步验证42例患者和5例健康对照中候选miRNA的异常表达。预测miRNA靶基因并生成蛋白质-蛋白质相互作用网络；此外，对基因本体论（GO）术语和京都基因与基因组百科全书（KEGG）通路中的靶基因进行功能富集分析。进行Kaplan-Meier曲线和Log-rank分析以及多变量Cox回归分析，以评估候选miRNA与患者生存的相关性。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miRNA，包括13种下调的miRNA和2种上调的miRNA。高级别胶质瘤中miR-374a的表达明显低于低级别胶质瘤（倍数变化，-4.43；P=0.027）。miR-374a的表达水平随着胶质瘤病理级别的增加而逐渐降低。采用Pearson卡方检验确定miR-374a表达与几种临床病理因素的相关性。此外，miR-374a的低表达被确定为独立的预后标志物，并且与总生存期显著相关（P=0.0213）。GO和KEGG通路分析表明，miR-374a的靶基因可能参与RNA聚合酶II启动子和mTOR信号通路的调控。通过蛋白质-蛋白质相互作用网络分析还鉴定出四个枢纽基因（）。总之，本研究表明，miR-374a可作为一种有前景的预后生物标志物，用于筛查高危人群和评估胶质瘤患者的预后。
