Expression And Significance Of Isocitrate Dehydrogenase1(IDH1) In Human Glioma

Objective:To discuss isocitrate dehydrogenase isoenzyme1(IDH1) genemutations expression mechanism in gliomas by Determining IDH1normalenzyme activity and protein content in gliomas which belong to WHO grade IIand grade III.Methods:56cases of glioma tissue samples were taken fromneurosurgery specimens in the Second Hospital of Hebei Medical Universityfrom July2012to December2013.Pathological diagnosis by the hospitalpathology department in WHO brain tumor classification standard. Thosesamples included10cases of astrocytomas (WHO grade II),12cases ofoligodendrogliomas (WHO grade II),5cases of oligoastrocytomas (WHOgrade II),15cases of anaplastic astrocytomas (WHO grade III),14cases ofanaplastic oligodendrogliomas (WHO grade III). Also taking brain traumacraniotomy in normal brain tissue (frontal and temporal lobes)5cases ascontrols. All tumor samples and normal brain tissue specimens were quicklyinto liquid nitrogen and stored at-80℃. The IDH1normal enzyme activitywas detected in all specimens by Using a method of ELISA (enzyme-linkedimmunosorbent assay) named the double antibody sandwich. The specimensabove were divided into three groups: Normal brain tissue group, WHO gradeII and III glioma group. Using the method of Western Blot to determine IDH1enzyme protein content of3groups of specimens Simultaneously and drewthe gray values corresponding protein content of samples. The data wereanalyzed by SPSS13.0.Results:1Enzyme activityThe experimental samples were detected by the ELISA for value ofenzyme activity.Taking the activity In normal brain tissue group as a standard value range, The value of all activity in the tumor tissue into the low and highactivity groups, Values are expressed in means±standard deviation: Normalbrain tissue group (n=5) was80.297±3.357; low activity group (n=35) was48.755±6.837; high active group (n=21) was132.246±14.887. The abovethree pairwise comparisons were statistically significant(P<0.05). The numberof cases in the low activity group was35, accounting for62.5%of the totalnumber of cases of gliomas.2Enzyme contentUsing the Western Blot method for the determination of IDH1enzymecontent of specimens. Values are expressed in means±standard deviation.Normal brain tissue group (n=5) was0.2609±0.0653, WHO grade II gliomagroup(n=27) was0.4577±0.8321,WHO grade III glioma group(n=29) was0.7110±0.0774. The above three pairwise comparisons were statisticallysignificant(P<0.05).3Analysis of correlation between activity and protein content of IDH1enzymeCalculated using the Pearson correlation analysis, the correlationcoefficient of WHO grade II gliomas was0.009; the correlation coefficient ofWHO grade III gliomas was0.201； the correlation coefficient of WHO gradeII and III gliomas was0.071, so the correlation between activity and proteincontent of IDH1enzyme was not obvious.Conclusions:1Compared with the normal control group, there is significant differencein IDH1normal enzyme activity of the glioma group.62.5%of the totalsamples,whose enzyme activities were lower than normal brain tissue.37.5%were higher than normal brain tissue. The result is consistent with the IDH1mutation rate in many current researches on related subtypes of gliomas. Thegliomas with IDH1normal activity decreased presence contain IDH1mutations can be considered.2Compared with the normal control group, IDH1enzyme proteincontent was significantly increased in glioma group,and among these measured gliomas, IDH1enzyme protein content in most WHO grade IIgliomas is higher than that in WHO grade III gliomas. The correlationbetween enzyme protein expression with glioma grade suggestd malignancylevel affect the IDH1enzyme protein content to some extent.3In glioma tissue, there was no significant correlation between the levelof IDH1normal activity and the level of the enzyme protein conten. ItPrompts the gene expression of IDH1mutation reduces IDH1normalenzyme activity,but it is not the decisive factor in determining the enzymeprotein content of IDH1.This shows that all aspects of complex regulatorymechanisms exists in the IDH1gene expression in the tumor tissue.