Investigation of the prognostic significance and mechanism of CIP2A expression in glioma patients
Objective To investigage the expression of cancerous inhibitor of protein phosphatase 2A(CIP2A)in gliomas and its impact on the patient's clinical prognosis,as well as its influence and mechanism on tumor cell migration and invasion.Methods CIP2A mRNA expression data in the brain gliomas and clinical data of these glioma patients were obtained from Chinese Glioma Genome Atlas(CGGA).Subsequently,67 samples from patients with glioma admitted to Department of Neurosurgery,the Second People's Hospital of Guiyang from January 2016 to October 2018 were selected in this study,and the expression levels of CIP2A in tumor tissues were detected using immunohistochemical staining methods.Based on data from the CGGA database,CIP2A mRNA expression in glioma patients with different gender,age,World Health Organization(WHO)grading,isocitrodehydrogenase(IDH)mutation statuses,1p/19q co-deletion statuses,and primary-recurrent-secondary(PRS)type were compared.Kaplan-Meier survival analysis,univariate and multivariate Cox analysis and receptor operating characteristic(ROC)curve analysis were used to evaluate the prognostic value of CIP2A in glioma patients.The siRNA interference was used to knock down CIP2A expression in U87 and U251 cells.Real-time quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression level of CIP2A mRNA in U87 and U251 glioma cells.Scratch test and transwell assay were used to analyze the effects of CIP2A on cell migration and invasion.Western blot was used to detect expression level of CIP2A,E-Cadherin,matrix metalloprotein(MMP)2 and MMP9 in U87 and U251 cells.Results In CGGA database,the expression of CIP2A was significantly upregulated in glioma tissues and elevated with WHO grading increased successively(F=49.32,P＜0.001).The overall survival of patients with low expression of CIP2A was significantly longer than that of patients with high expression of CIP2A(CGGA database:P＜0.001;Clinical data:P＜0.05).In CGGA database,high CIP2A expression was significantly related to PRS(tumor recurrent and secondary),IDH wild-type and 1p19q non-codeletion(all P＜0.001).ROC curve analysis revealed that the area under the curve of CIP2A mRNA in predicting 1,3,and 5 year survival rates of glioma patients were 0.72、0.74 and 0.73.Multivariate cox regression analysis indicated that high CIP2A expression,advanced age,PRS(tumor recurrent and secondary)and high-grade tumors were the independent risk prognostic factors in glioma patients(all P＜0.001).The siRNA significantly reduced the mRNA and protein expression of CIP2A in U87 and U251 cells(both P＜0.05).In U87 and U251 cells with low expression of CIP2A,there was a significant decrease in both wound healing ability and the capabilities for migration and invasion(all P＜0.05).The expression of E-Cadherin in U87 and U251 cells with low expression of CIP2A was up-regulated,and the expression of MMP2 and MMP9 protein was down-regulated(all P＜0.05).Conclusions CIP2A is significantly overexpressed in glioma,which predicts poor prognosis of glioma and thus may be a potential prognostic marker of glioma.Furthermore,the low expression of CIP2A may inhibit the migration and invasion of glioma cells through the suppression of epithelial-mesenchymal transition(EMT)pathway.
GliomaPrognosisCell invasionCell migrationCancerous inhibitor of protein phosphatase 2 A
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