Department of Neurosurgery, The First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710061, PR China.
The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, 710004, PR China.
Pathol Res Pract. 2019 Oct;215(10):152557. doi: 10.1016/j.prp.2019.152557. Epub 2019 Jul 23.
Aurora kinase B (AURKB) and Ubiquitin conjugating enzyme E2C (UBE2C) are involved in tumorigenesis of gliomas and other malignancies as well, but their clinicopathologic significance in gliomas is unknown and the prognostic value of combined expression of AURKB and UBE2C has not been explored. In this study, we investigate the correlation between glioma prognosis and combined expressions of AURKB and UBE2C thus to identify novel therapeutic targets and prognostic biomarkers for glioma patients.
AURKB was identified as one of the key candidate kinase-encoding genes in three different databases by using kinome-wide bioinformatic analysis. Afterwards, UBE2C was chosen as the most closely relevant genes to AURKB according to Spearman correlation test. Then the expressions of AURKB and UBE2C at either transcriptome or protein levels were measured by quantitative Real-time PCR (qRT-PCR) or immunohistochemistry (IHC), respectively. Additionally, Kaplan-Meier analyses were conducted using data from TCGA, Rembrandt and our clinical center to investigate the clinical significance of AURKB and UBE2C. Furthermore, receiver operating characteristic (ROC) analysis was performed to evaluate the sensitivity and specificity of AURKB and UBE2C in predicting the outcomes of glioma patients. Moreover, survival data of patients who underwent post-surgical chemo/radio treatment were extracted and the Kaplan-Meier analyses were performed to investigate the correlation between treatment resistance and combined expressions of AURKB and UBE2C.
Both AURKB and UBE2C were significantly up-regulated in gliomas compared to normal brain tissues and the combined elevation of AURKB and UBE2C were strongly associated with histological classification in glioma. Moreover, overexpression of either AURKB or UBE2C strongly correlated to more severe overall survival. Notably, upregulation of these two genes revealed unfavorable outcomes (shorter overall survival and therapy resistance) in glioma patients with significant sensitivity and specificity.
Simultaneously elevated expressions of AURKB and UBE2C was strongly correlated to poor prognosis and therapy resistance in glioma, furthermore, our data suggest for the first time that the combination of AURKB and UBE2C overexpression could be highly sensitive prognostic markers and potential therapeutic targets for glioma patients.
极光激酶 B（AURKB）和泛素结合酶 E2C（UBE2C）都参与了胶质瘤和其他恶性肿瘤的发生，但其在胶质瘤中的临床病理意义尚不清楚，AURKB 和 UBE2C 联合表达的预后价值也尚未被探索。在这项研究中，我们研究了胶质瘤预后与 AURKB 和 UBE2C 联合表达之间的相关性，从而为胶质瘤患者确定新的治疗靶点和预后生物标志物。
通过激酶组全基因组生物信息学分析，在三个不同的数据库中确定 AURKB 为关键候选激酶编码基因之一。之后，根据 Spearman 相关检验，选择 UBE2C 作为与 AURKB 最相关的基因。然后，通过定量实时 PCR（qRT-PCR）或免疫组织化学（IHC）分别测量 AURKB 和 UBE2C 的转录本或蛋白质水平的表达。此外，使用 TCGA、Rembrandt 和我们的临床中心的数据进行 Kaplan-Meier 分析，以研究 AURKB 和 UBE2C 的临床意义。此外，进行了接收者操作特征（ROC）分析，以评估 AURKB 和 UBE2C 预测胶质瘤患者结局的敏感性和特异性。此外，提取接受手术后化疗/放疗的患者的生存数据，并进行 Kaplan-Meier 分析，以研究 AURKB 和 UBE2C 联合表达与治疗抵抗之间的相关性。
与正常脑组织相比，AURKB 和 UBE2C 在胶质瘤中均显著上调，AURKB 和 UBE2C 的联合升高与胶质瘤的组织学分类密切相关。此外，AURKB 或 UBE2C 的过表达与更严重的总生存期显著相关。值得注意的是，这两个基因的上调在具有显著敏感性和特异性的胶质瘤患者中揭示了不利的结局（更短的总生存期和治疗抵抗）。
AURKB 和 UBE2C 的同时高表达与胶质瘤的不良预后和治疗抵抗密切相关，此外，我们的数据首次表明，AURKB 和 UBE2C 过表达的联合可能是高度敏感的预后标志物和潜在的治疗靶点，用于胶质瘤患者。
