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Study On The Correlation Between IDH1 Gene Mutation And MTOR Expression In Human Gliomas Prognosis

Posted on:2018-10-25Degree:MasterType:Thesis
Country:ChinaCandidate:J B BaiFull Text:PDF
GTID:2334330515954327Subject:Neurosurgery
Abstract/Summary:PDF Full Text Request
Background and Object:As the most common intracranial malignant tumors,Glioma account for about70% of all primary central nervous system tumors.In recent years,with the continuous development of microsurgical techniques and a variety of treatment models,more and more glioma patients have been timely and effective treatment,but the prognosis of most patients is still not very ideal.At present,there are still many difficult questions about the mechanism of glioma occurrence and the judgment of its prognosis.Looking for different genes in different gliomas is the direction of development of glioma from molecular level.Parsons found that IDH1 gene mutations were higher in younger patients and glioblastomas in patients with genomic analysis of 22 cases of glioblastoma in 2008,and it was associated with an increase in overall survival,suggesting that IDH1 mutations is of great significance in the development of human glioma.Subsequent studies have shown that IDH1 gene mutation in the II-? grade glioma in the incidence of about 60-90%,indicating that IDH1 gene mutation in the human brain is universal.However,although some patients have IDH1 gene mutation,the survival is relatively short,some patients who did not occur IDH1 gene mutation have relatively long survival,this indicating that is not comprehensive to determine the prognosis of patients with IDH1 gene mutation.Mammalian target of rapamycin(m TOR),is an atypical serine / threonine protein kinase,also an important signaling pathway of transduction molecules,can participate in a variety of pathology and physiological processes,It play a bridge role in gene expression and cell proliferation.However,the occurrence and development of glioma contains a number of factors,simply by m TOR expression of glioma assessment also have a certain one-sided.Therefore,we try to analyze the prognosis of patients with glioma by analyzing the mutation of IDH1 gene and m TOR expression in gliomas,and provide a new idea and method for the prognosis evaluation of glioma patients.In view of the above background,we try to analyzed the correlation between IDH1 gene mutation and m TOR expression in gliomas by examining the association of IDH1 gene mutation and m TOR expression in 45 newly diagnosed glioma patients,and analyzed the differences and correlations,and then to study its clinical significance and prognosis of glioma patients.Methods:Collection of Chinese People's Armed Police Force General Hospital Neurosurgery January 2012 to 2016.There were 45 cases of intracranial gliomas treated by operation in June,including 24 males and 21 females,aged 8-68 years(mean 42.7 years).The age group was divided into two groups according to WHO regulations.(Age ? 50 years),older group(age> 50 years).According to the WHO classification of central nervous system tumors in 2007,there were 2 cases of grade ? gliomas,29 cases of grade II gliomas,10 cases of grade ? gliomas and 7 cases of grade III gliomas.According to the pathological type of tissue source classification: derived from the astrocytes of hair cell astrocytoma in 2cases,15 cases of astrocytoma,astrocytic cell tumor in 6 cases: from oligodendrocytes Glioblastoma in 5 cases,metaplastic oligodendroglioma in 9cases: primary glioblastoma in 3 cases,5 cases of secondary glioblastoma.Above specimens were confirmed by the Institute of Pathology,medical records complete.All the pathological specimens of this group were fixed in 10%formalin immediately after resection.The real-time fluorescence quantitative PCR was used to detect the mutation of IDH1 gene.The expression of m TOR was detected by semi-quantitative rabbit immunohistochemistry.The experimental data were analyzed by SPSS20.0 software.The chi-square test was used to analyze the relationship between IDH1 gene mutation and m TOR expression in different age,sex and pathological grade.Spearman rank correlation analysis was used to analyze the correlation between IDH1 gene mutation and m ROR expression.The median survival time and survival rate were measured by KaplanMeier method.The corresponding survival curves were drawn from each group and analyzed by log-rank method.P <0.05 for the difference was statistically significant.Results:1.45 cases of glioma patients with IDHl mutation in 21 cases,the overall positive table 46.7%,in different age groups were not statistically significant(P> 0.05),in different pathological grades were not statistically significant(P >0.05).There was no significant difference between different sexes(P> 0.05).The median PFS was 17.6months in the IDHl mutation group and 14.4 months in the wild group(P <0.05),the difference was statistically significant.The median OS time was 18.2 months in the IDHl mutant group and 15.4 months in the wild group(P <0.05),the difference was statistically significant.2.45 cases of glioma patients with m TOR expression in 26 cases,the overall positive expression rate of 57.8%.There was no significant difference between different age(P>0.05).There was no significant difference between different pathological grades(P> 0.05),But with the pathological grade increased,the positive expression rate increased too.There was no significant difference between different sexes(P> 0.05).The median FPS of the m TOR positive expression group was 14.3 months and the negative group was 17.7 months(P <0.05),the difference was statistically significant;the median OS was 15.4 months in the m TOR positive group and 18.8 months in the negative group <0.05),the difference was statistically significant.3.In this group,45 cases were divided into 4 groups,m TOR expression and IDH1 gene mutation in 9 cases(compiled for group 1),m TOR expression and IDH1 mutations in 17 cases(for group 2),m TOR not expressed IDH1 gene mutations in 15cases(group 3),m TOR was not expressed and IDH1 gene mutation in 4 cases(group 4),the difference between the four groups was statistically significant(P<0.05),There was significant difference between group 3 and group 1(P = 0.024).There was significant difference between group 3 and group 2(P = 0.048),and there was significant difference between group 3 and group 4(P=0.008).Group 1 and group 2 were statistically significant(P=0.043).In group 1 and group 4 there was no significant difference between the two groups(P=0.237).There was no significant difference between group 2 and group 4(P=0.631).There was a statistically significant correlation between IHD1 gene mutation and m TOR expression(P <0.05).Conclusion:1.There was a significant correlation between the IDH1 gene mutation and the survival time of the glioma tissue.The median survival time of IDHl mutation was significantly longer than that of the negative group,which was correlated with the age of the patients and had no correlation with sex and pathological grade.2.The expression of m TOR in glioma tissue was significantly correlated with the survival time of patients.The survival time of m TOR positive expression was significantly shorter than that of negative expression.There was no correlation with age(P> 0.05),sex and pathological grade,but the positive rate The higher the higher(P>0.05),3.There was statistical relevance bewteen IHD1 gene mutation and m TOR expression.The prognosis of patient who had m TOR expression and IDH1 gene mutation was better than other patients,the prognosis of patient who had m TOR unexpressed and IDH1 gene mutation was better than the patients who had m TOR expression and IHD1 unmutated.MTOR expression and IDH1 gene mutations can be used as prognostic indicators of glioma patients.
Keywords/Search Tags:Gliomas, IDH1 gene mutation, phosphatidylionl 3-kinase-related kinase, Prognosis, Malignant Gliomas
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