Evidence Quality Evaluation And Molecular Marker Study Of Glioblastoma

Objective As the most common form of malignant tumour in central nervous system,glioblastoma has very poor prognosis.This study aims to evaluate state-of-the-art treatment methodologies of glioblastoma via a series of evidence based research and laboratorial verification,and elaborate on the significance of molecular markers to serve as a strong hint to its prognosis.(1)Assess the methodology and reporting quality of randomized controlled trials,systematic reviews/meta analysis,and clinical practice guidelines for glioblastoma by the related checklist;(2)Evaluate the overall survival and progression-free survival of glioblastoma by seven treatment regimens using a network meta-analysis;(3)Screen the up-regulated expression gene and down-regulated expression gene using the gene chip data of glioblastoma on the AffyU133 a platform,and verify the differentially-expressed genes by real-time fluorescent quantitative PCR;(4)Analyze the expression and clinical significance of EGFR,IDH1,ATRX,P53,MGMT,VEGF and Ki67 in glioblastoma.Methods(1)Obtain randomized controlled trials,meta-analysis,and clinical practice guidelines for glioblastoma treatment by retrieving the primary foreign language database,and evaluate the reporting quality and methodological quality by using relevant scales.Analyze the data using STATA12.0 and Meta analyst software;(2)Perform randomized controlled trials of radiotherapy or chemotherapy combined with radiotherapy for glioblastoma by retrieving the primary foreign language database,screening and making selection according to pre-established inclusion and exclusion criteria,evaluating the quality of randomized controlled trials,and recommending grading of the measured indicators.Perform statistical analysis using WinBugs and STATA 12.0 software;(3)Analyze the patient survival rate by using Kaplan-Meier curve from the AffyU133 a platform glioblastoma gene chip data,and at the same time,use the R language survival package,survival ROC software packageand glmnet software package to perform univariate survival analysis,multivariate Cox regression analysis,generated ROC curve and LASSO analysis.Use real-time PCR to validate genes with large differences in multiples;(4)Detect the expression of IDH1,EGFR,ATRX,P53,MGMT,VEGF and Ki67 in GBM by immunohistochemistry.Result(1)The reporting and methodological quality of randomized controlled trials,systematic reviews/Meat analysis,and clinical practice guidelines for glioblastoma have certain limitations;(2)The results of the network meta-analysis showed that the overall survival was longer in the radiotherapy + temozolomide regimen than in the radiotherapy regimen alone;Nimustine + cisplatin + radiotherapy+ temozolomide treatment regimen has a lower incidence rate of neutropenia than radiotherapy + temozolomide and radiotherapy alone;the frequency of thrombocytopenia in radiotherapy + bevacizumab + irinotecan is lower than bevacizumab + radiotherapy + temozolomide;(3)The expression of ABCA1 was up-regulated,and the expression of ASIC2,KCNJ6,NPY,HOMER1,GPC5 and KCNMB4 were down-regulated.Real-time fluorescent quantitative PCR confirmed that the difference in the expression of NPY,ASIC2 and ABCA1 was statistically significant;(4)Expression of IDH1,EGFR,ATRX,P53,MGMT,VEGFand Ki67 affect both overall survival and progression-free survival in patients with glioblastoma.Conclusion(1)In the future,randomized controlled trials of glioblastoma should focus on the correct reporting and implementation of adverse outcomes,research design methods,and so on.The systematic review /Meat analysis of the glioblastoma requires further improvement in the quality of the report.Clinical practice guidelines for glioblastoma should be rigorously developed and reported based on the best available evidence;(2)Adding other targeted drugs,especially bevacizumab and nimustine,to radiotherapy + temozolomide in the treatment of glioblastoma can prolong both survival and progression-free survival,but adverse events can also occur;(3)NPY,ASIC2 and ABCA1 genes are associated with prognosis of glioblastoma;(4)High expression of IDH1,ATRX,VEGF and Ki67,and low expression of EGFR,P53 and MGMT all affect the overall survival and progression-free survival of glioblastoma.