Xia Xiangping, Cao Fang, Yuan Xiaolu, Zhang Qiang, Chen Wei, Yu Yunhu, Xiao Hua, Han Chong, Yao Shengtao
Department of Cerebrovascular Disease, The First Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
Department of Stroke Unit and Neurosurgery, The First People's Hospital of Zunyi, Zunyi, Guizhou, China.
PeerJ. 2019 Nov 19;7:e7974. doi: 10.7717/peerj.7974. eCollection 2019.
As the most aggressive brain tumor, patients with glioblastoma multiforme (GBM) have a poor prognosis. Our purpose was to explore prognostic value of Polo-like kinase 2 (PLK2) in GBM, a member of the PLKs family.
The expression profile of PLK2 in GBM was obtained from The Cancer Genome Atlas database. The PLK2 expression in GBM was tested. Kaplan-Meier curves were generated to assess the association between PLK2 expression and overall survival (OS) in patients with GBM. Furthermore, to assess its prognostic significance in patients with primary GBM, we constructed univariate and multivariate Cox regression models. The association between PLK2 expression and its methylation was then performed. Differentially expressed genes correlated with PLK2 were identified by Pearson test and functional enrichment analysis was performed.
Overall survival results showed that low PLK2 expression had a favorable prognosis of patients with GBM (-value = 0.0022). Furthermore, PLK2 (HR = 0.449, 95% CI [0.243-0.830], -value = 0.011) was positively associated with OS by multivariate Cox regression analysis. In cluster 5, DNA methylated PLK2 had the lowest expression, which implied that PLK2 expression might be affected by its DNA methylation status in GBM. PLK2 in CpG island methylation phenotype (G-CIMP) had lower expression than non G-CIMP group ( = 0.0077). Regression analysis showed that PLK2 expression was negatively correlated with its DNA methylation ( = 0.0062, Pearson = -0.3855). Among all differentially expressed genes of GBM, CYGB ( = 0.5551; < 0.0001), ISLR2 ( = 0.5126; < 0.0001), RPP25 ( = 0.5333; < 0.0001) and SOX2 ( = -0.4838; < 0.0001) were strongly correlated with PLK2. Functional enrichment analysis results showed that these genes were enriched several biological processes or pathways that were associated with GBM.
Polo-like kinase 2 expression is regulated by DNA methylation in GBM, and its low expression or hypermethylation could be considered to predict a favorable prognosis for patients with GBM.
多形性胶质母细胞瘤（GBM）是最具侵袭性的脑肿瘤，其患者预后较差。我们的目的是探讨PLK家族成员Polo样激酶2（PLK2）在GBM中的预后价值。
从癌症基因组图谱数据库获取GBM中PLK2的表达谱。检测GBM中PLK2的表达。绘制Kaplan-Meier曲线以评估GBM患者中PLK2表达与总生存期（OS）之间的关联。此外，为了评估其在原发性GBM患者中的预后意义，我们构建了单变量和多变量Cox回归模型。然后分析PLK2表达与其甲基化之间的关联。通过Pearson检验鉴定与PLK2相关的差异表达基因，并进行功能富集分析。
总生存期结果显示，低PLK2表达对GBM患者有良好的预后（P值 = 0.0022）。此外，通过多变量Cox回归分析，PLK2（HR = 0.449，95% CI [0.243 - 0.830]，P值 = 0.011）与OS呈正相关。在簇5中，DNA甲基化的PLK2表达最低，这意味着PLK2表达可能受其在GBM中的DNA甲基化状态影响。CpG岛甲基化表型（G-CIMP）中的PLK2表达低于非G-CIMP组（P = 0.0077）。回归分析表明，PLK2表达与其DNA甲基化呈负相关（P = 0.0062，Pearson r = -0.3855）。在GBM的所有差异表达基因中，CYGB（r = 0.5551；P < 0.0001）、ISLR2（r = 0.5126；P < 0.0001）、RPP25（r = 0.5333；P < 0.0001）和SOX2（r = -0.4838；P < 0.0001）与PLK2高度相关。功能富集分析结果表明，这些基因富集于与GBM相关的多个生物学过程或途径。
在GBM中，Polo样激酶2的表达受DNA甲基化调控，其低表达或高甲基化可被视为GBM患者预后良好的预测指标。
