The Correlation Study Of Isocitrate Dehydrogenase Gene Mutation And Vascular Endothelial Growth Factor In Glioma

Objective: Glioma has the highest morbidity in central nervous system malignant tumor, accounting for about 40%~50% of intracranial tumor. Our country has a lot of gliomas disease patients, each year the number of death caused by glioma is very huge. Because glioma has invasive growth ability, the treatment is very difficult. It cause a seriously threatens of Chinese people’ health. Any kinds of tumor are caused by genetic mutations or variations in chromosome structure cell, so the research in order to identification of cancer related gene become the central of the field.In 2008, Parsons sequenced 20% protein coding genes, determined the presence of amplifications and deletions using high-density oligonucleotide arrays, and performed gene expression analyses using next-generation sequencing technologies in 22 human tumor samples. They found recurrent mutations in the active site of isocitrate dehydrogenase1(IDH1) in 12% of GBM patients. Someone pointed out that after IDH1 gene mutation in glioma can increase the expression of vascular endothelial growth factor(VEGF) and VEGF can enhance tumor’s nutrition to facilitate adaptive survival, proliferation and metastasis. But the principle lack related cases data support.In order to prove wheather IDH1 mutations will enhance VEGF expression or not, we have detected different levels, different pathological type of glioma and normal brain tissue’s IDH1 mutations and VEGF protein expression. The study can do something to illuminate the mechanism how IDH1 gene mutations cause glioma, to provide new thought and theoretical basis for targeted therapy for gliomas IDH1 gene mutations and antiangiogenesis therapy.Methods:We have collected 57 cases who do neurosurgery to removal brain glioma in hebei medical university ’s second hospital during January 2013 to October 2014.According to the 2007 WHO classification of the central nervous system tumors, wo have collected II grade glioma 18 cases, III grade glioma 19 cases, IV grade glioma 20 cases. According to the pathological type classification: astrocytes and anaplastic astrocytoma 21 cases, oligodendroglioma and anaplastic oligodendroglioma 16 cases, 20 cases of glioblastoma. All the cases have complete medical records and have been confirmed by pathology. The other 11 normal cases were from patient who need Intracranial decompression surgery. All glioma patients were first treated, do not have any radiation or chemotherapy treatment before operation. All specimens were put in10% formalin immediately when the tumour cut off. We use immune histochemical methods IHC and immunofluorescence technique to detect IDH1 R132 H, VEGF expression in brain glioma and normal brain tissue. The experimental data using SPSS13.0 software for statistical analysis.Results:1 IDH1 mutations and the expression of VEGF protein can not be detected in the normal brain tissue.2 The IDH1 gene mutation rate in the II, III and IV grade glioma is: 61.1%, 63.2%, 63.2% respectively, the comparison between each group have statistical significance, except II and III glioma group.3 The VEGF expression positive rate in II III and IV grade glioma is: 44.4%, 57.9%, 85.0% respectively, having statistically significant.4 The IDH1 gene mutation rate in astrocytoma, oligodendroglioma and glioblastoma is 57.1%, 68.8%, 10% respectively, the comparison bet-ween each group have statistical significance, except in astrocytoma, oli-godendroglioma group.5 The VEGF positive rate in astrocytoma, oligodendroglioma and gl ioblastoma is 57.1%, 43.8%, 85% respectively, the comparison between ea-ch group have statistical significance, except in astrocytoma, oligoden dr-oglioma group.6 The VEGF positive rate in IDH1 mutant and wild type of astrocytoma is 91.67% and 11.1%, respectively; The VEGF positive rate in IDH1 mutant and wild type oligodendroglioma is 63.64% and 0%, respectively; The VEGF positive rate in IDH1 mutant and wild type of glioblastoma is 100% and 83.33%, respectively. the comparison between each group have statistical significance, except glioblastoma group.7 The VEGF positive rate of all the glioma in IDH1 mutant and wild type is 80% and 50%, respectively, having statistically significant and Pearson C is 0.295.Conclusion:1 The IDH1 R132 H mutation rate is different in the different pathological types of glioma, in astrocytoma and oligodendroglioma the IDH1 R132 H mutation rate is about 65%, in iprimary glioblastoma the mutation rate is only 10%.2 The VEGF expression’s positive rate have statistically significant in different pathological levels of glioma, and the positive rate is low i n the lower grade gliomas, is higher in high grade glioma. The impro ve-ment of pathological level is associated with the malignant degree of tumor.3 The IDH1 gene mutation have strong correlation with VEGF expression, IDH1 gene mutations can promote VEGF expression, but the VEGF is regulated by the many factors.