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The Effect Of IDH Mutation On The Proliferation Activity Of Low-grade Glioma And Prognosis Analysis

Posted on:2019-08-11Degree:MasterType:Thesis
Country:ChinaCandidate:Y Z WangFull Text:PDF
GTID:2404330566493322Subject:Surgery
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Objective:Glioma is one of the most common primary tumors in the nervous system.and it is difficult to predict its future development after discovery.Through recent medical research,it has been found that mutation activity of isocitrate dehydrogenase(IDH)has a certain influence on the prognosis of gliomas.IDH mutations generally refer to genetic changes in WHO grade II-III gliomas,but it is unclear why IDH mutations cause glioma growth.Subjects and Methods:The study collected and tested the specimens for glioma patients in our hospital,select tumor-enriched tissue by tissue paraffin section and routine HE staining.Then analyze the IDH1/2 mutation of glioma by sequencing.Use Integrative Genomics Viewer to analyze the copy number of different chromosomes in gliomas.Determine whether there is a 1p/19 q joint deletion in the corresponding glioma patient.Thus,278 lower-grade gliomas were divided into three groups: IDH mutation without 1P/19 q joint deletion group,IDH mutation with 1p/19 q joint deletion group,and IDH wild-type group.Perform correlation analysis of histological types,grades of three groups of gliomas and other genetic changes by onco printer online analysis tool.Meanwhile,the patient's progression-free survival and overall survival were analyzed using SpSS16.0.To investigate the effect of IDH mutations on microvessel density in low grade gliomas,we examined the expression of IDHI(R132H)in Ki-67,CD34,and lower grade glioma tissue by immunohistochemical staining.Then,using the method of zhen,the Ki-67 labeling index was expressed as the percentage of Ki-67-positive tumor cells to evaluate the microvessel density.Simultaneous analysis of Ki-67 marker index,microvessel density,and lower grade glioma grading.Results:Through the analysis of our hospital glioma specimens of paraffin IDH mutation results show that the IDH mutation(0/21)of the test is not found in the WHOI grade glioma,52.8%(47/89)for IDH mutation rate in the level III WHO glioma in the WHO grade II mutation rate was 50.3%(70/139),the secondary glioblastoma(WHO grade IV)the mutation rate is 46.7%(7/15),while in primary glioblastoma(WHO grade IV)mutation rate is only 4.1%(5/121).The above results indicated that patients with secondary glioblastoma,WHOII and WHOIII glioma were the main source of IDH mutations,about 50% mutation rate,slightly lower than those reported in foreign countries.The data of patients with low grade glioma in TCGA database were analyzed,and the IDH mutation was accompanied by a glioma with 1 P/19 q.For patients according to classifying,molecular classification results showed that the prognosis is best IDH mutation with 19 q 1 P/joint lack of gliomas,prognostic effect times IDH mutation is not associated with 19 q 1 P/loss of heterozygosity of gliomas,the worst prognosis is IDHI wild type gliomas.Follow-up study,the results showed that IDHI(R132H)expression level in the WHO II-there are differences in the level III glioma,and glioma cells of microvascular density and Ki-67 labeling index with IDHI(R132H)expression level increased significantly increased.However,there was no significant difference between the non-mutant and IDH mutated glioma ki-67 li in the same grade glioma patients.However,IDH wild-type glioma at the corresponding level was significantly lower than that of IDH mutated glioma microvascular density.The above results indicated that the proliferation of tumor cells was not significantly affected by IDH mutations,but had a significant effect on the angiogenesis of the lower grade glioma.In summary,the IDH mutation status is closely to other genetic changes and can be used as a good predictor of prognosis in glioma patients.At the same time,IDH mutations promote the proliferation of gliomas and study the proliferation of glioma cells.There are also certain values in terms of migration,invasion,etc.It is worth further research in the future.
Keywords/Search Tags:isocitrate dehydrogenase mutation, glioma
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