The Effect Of IDH1 Mutation On Prognostic Survival Time Of Glioma And Its Possible Mechanism

Objective :Having analyzed the effect of IDH1 mutation on the survival time of glioma and to explore its possible mechanism,it can provides a new idea and direction for studying the mechanism of IDH1 in improving the prognosis of glioma and the targeted therapy of glioma.Methods: data collection: from January 2010 to May 2017,a total of 63 cases of human glioma were treated with paraffin wax in the neurosurgical department of the first affiliated Hospital of University.According to the WHO classification of central nervous system tumors in 2013,there were 2 cases of gradeⅠ,25 case of grade II gliomas and 24 cases of grade III gliomas,12 cases of grade IV gliomas.According to the histological types,27 cases of astrocytoma and anaplastic astrocytoma,24 cases of oligodendrocytoma and anaplastic oligodendrocytoma and 12 cases of Glioblastoma.All of above specimens have complete medical records and have been confirmed by the Department of Pathology of our hospital.The normal brain tissues of 5 patients with evacuation of intracranial hematoma collected for the control group.Patients with glioma did not undergo any anti-tumor therapy such as radiotherapy and chemotherapy before operation.The mutation of IDH1 was detected by PCR fluorescence probe method and the expression intensity of IDH1 and EGFR and CD34 was detected by immunohistochemistry.Results: The mutation of IDH1 gene was detected by immunohistochemistry and PCR-fluorescence probe method in 63 tissue samples.In only one case,the results were inconsistent,the results of gene test were negative and immunohistochemical staining was positive.The expression of IDH1 and EGFR was not found in 5 cases of normal brain tissue after intracranial decompression surgery,but a small amount of MVD was found.There were 35 cases of IDH1 mutation in all glioma specimens,all of which were located at the R132 H locus,28 cases were not mutated,among them there were 0 cases of grade Ⅰ,15 cases of grade Ⅱ(60%),11 cases of grade Ⅲ(45.8%),and 2 cases of grade Ⅳ(16.6%).There was no significant difference between Ⅱ and Ⅲ.But the mutation rate of low-grade glioma(Ⅰ,Ⅱ)was higher than that of high-grade glioma(Ⅲ,Ⅳ)(P<0.05).The median onset age of patients with IDH1 mutation was 38.89 ±9.86 years and wild type was 49.46±15.42years(t test,P<0.05).IDH1 mutation is not related to sexual.There were 43 cases(65%)with positive expression of EGFR,including 1 case of grade Ⅰ,13 cases of grade Ⅱ(52%),19 cases of grade Ⅲ(79.1%),and 10 cases of grade Ⅳ(83.3%),there was no significant difference between Ⅱ and Ⅲ(P<0.05)The difference between the lower grade group(51.8%)and the high grade group(80.5%)was statistically significant(P=0.018<0.05).The median survival time of the glioma patients with IDH1 mutation was 48 months,which was significantly longer than the 17 months of the wild type of IDH1.The difference was statistically significant(P =0.007 < 0.05).The overall median survival time was 33 months.The expression of IDH1 was negatively correlated with the expression of EGFR,(the correlation coefficient was-0.37 and 0.003 < 0.05).The median survival time was 22 months in EGFR positive group and 62 months in negative group.There was a positive correlation between MVD count and EGFR expression in glioma patients(the correlation coefficient was 0.499 P < 0.05).There was a significant difference in MVD count between negative and positive EGFR expression groups(24.51 ±15.12 vs 45.38 ±19.32 t test t=-4.24 P=0.000).There was significant difference in MVD count between IDH1 negative group and positive group(P=0.045<0.05,t=2.04).The MVD of high grade glioma(48.84 ±19.60)was higher than that of low grade glioma(25.30 ±12.52),and the difference of MVD count of different grade glioma was statistically significant(t test P < 0.05).Conclusion:1、the results of IDH1 mutation detected by PCR fluorescence probe method and immunohistochemistry method were basically the same.Detection of IDH1 mutation by immunohistochemical method can replace PCR fluorescence probe method as a routine screening method.As a routine screening method.2、 glioma patients with IDH1 mutation have longer survival time.3、IDH1 is involved in the early development of the tumor.It may play a role by down-regulating the expression of EGFR and inhibiting its downstream signaling pathway,which may affect the occurrence,development and prognosis of tumor.