Combined elevation of AURKB and UBE2C predicts severe outcomes and therapy resistance in glioma

Abstract Objectives 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. Methods 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. Results 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. Conclusion 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.