Screening Genes Of Long-term Glioblastoma By Bioinformatics

Background:Glioblastoma is the most common and malignant tumor of the central nervous system in adults.Despite of the use of surgical resection,radiotherapy and temozolomide chemotherapy standard treatment,most patients have poor prognosis.But little part of patients have relatively good prognosis,The median survival time was 24 months or more.Previous research have found that,treatments sensitivity and prognosis of GBM patients were associated with variety of molecular markers.Looking for the factors that relevanted with glioblastoma prognostic is of great significance for improve the survival rate of GBM patients.The bioinformatics could carry on the massive analyses in the database for homology analysis,similarity analysis and so on.Giving us access to research regulation of genes at the whole genome level.Therefore,the application of bioinformatics technology has greatly promoted the development of basic medical research.Objective:This paper is to Screen for genes related to the prognosis of patients with GBM,investigate the clinical features and the expression of tumor cells in GBM patients with long-term survival,improving the treatment effect of GBM patients and providing basis for prognosis evaluation.Methods:Firstly,WebArrayDB is used to analyze the microarray data,and we screened the first 100 genes from GEO database which are significantly associated with glioblastoma patients who have long survival(LTSs)and short survival(STSs),and then Contrastive analyzed with the candidate gene in TCGA and REMBRANDT database,finally,we screened out 3 main genes that influence the prognosis of patients:Fibulin-4,IGFBP-2 and CHI3L1.Secondly,we collected the FFEP of 77 GBM patients,extracted the DNA and RNA,qMSP was used to detect the methylation status of MGMT promoter in tumor,qPCR was used to detect the expression of these genes.It is of great clinical significance to study the correlation between gene and prognosis of patients,and to provide basis for the evaluation of prognosis of GBM.Results:According to Integrated analysis of Microarray data we concluded that Fibulin-4,IGFBP-2 and CH3L1 were closely related with the survival time of patients with glioblastoma.In our experimental study,MGMT promoter methylation rate was higher in LTS group(73.3%)than STS group(38.7%).Difference between the two groups was statistically significant(p<0.01).Expression levels of the mRNAs of these 3 genes were higher in the GBM samples than in normal brain samples(p<0·01)and these 3 genes were significantly upregulated in STSs compared to the levels in LTS samples(p<0.01).Multivariate analysis showed that the expression of Fibulin-4 and IGFBP-2 were significant correlation with patient prognosis(p<0.05).Kaplan-Meier analysis showed that the expression patterns of Fibulin-4 and IGFBP-2 serve as independent prognostic indicators for overall survival(p<0.01 and p<0.05,respectively).Conclusion:Fibulin-4 and IGFBP2 are closely related to the prognosis of GBM patients,Their expression level can be used as a basis for evaluating the prognosis of patients.