Study On Expression And Correlation Of IDH And STAT1 In Astrocytic Tumors

Objective:Astrocytic tumors is a kind of brain tumor caused by astrocytes.Which are common primary tumor in the central nervous system.Isocitrate dehydrogenase(IDH)mutation,abnormal expression of signal transducer and activator of transcription1(STAT1)protein play an important role in the development of astrocytic tumors.This study aims to investigate the expression,clinical significance and prognostic value of the combination of IDH and STAT1 in astrocytic tumors,to analyze their roles and correlations in the development of astrocytic tumors.Methods:20 cases of cerebral hemorrhage tissue specimens and 110 cases of astrocytic tumors specimens were selected as the research objects,including 24 cases of pilocytic astrocytoma,35 cases of diffuse astrocytoma,24 cases of anaplastic astrocytoma and 27 cases of glioblastoma.Immunohistochemistry(IHC)En Vision two-step method was used to detect the expression of IDH1 and STAT1 in 110 cases of surgically resected astrocytic tumors and 20 cases of cerebral hemorrhage tissue,respectively.Furthermore,Sanger sequencing was used to detect IDH1/2 mutations in86 cases of WHO II～IV grade astrocytic tumors and relevant clinical data of the patients were collected for statistical analysis.Then,the expression of IDH and STAT1 in astrocytic tumors and their correlation,clinical significance and evaluate the prognosis of their combination were analyzed.Results:1.The expression of IDH1 and STAT1 in 110 cases of astrocytic tumors and 20 cerebral hemorrhage tissue was detected by immunohistochemistry,and the results were as follows: IDH1 was negatively expressed in cerebral hemorrhage tissue and pilocytic astrocytoma,and its positive expression rate was 58.8%(20/34)in diffuse astrocytoma,45.0%(9/20)in anaplastic astrocytoma,and 11.5%(3/26)in glioblastoma.The positive expression rate of IDH1 in invasive astrocytic tumors decreased with the increase of WHO histological grade,and the difference was statistically significant(P<0.05);STAT1 was positively expressed in cerebral hemorrhage tissue,and its positive expression rate was 66.7%(16/24)in pilocytic astrocytoma,47.1%(16/34)in diffuse astrocytoma,40.0%(8/20)in anaplastic astrocytoma,and30.8%(8/26)in glioblastoma.The positive expression rate of STAT1 decreased with the increase of WHO histological grade in astrocytic tumors and there was statistical significance(P<0.05).The expression of IDH was correlated with WHO histological grade and survival status(P<0.05),but not with age and gender(P>0.05),while the expression of STAT1 was correlated with survival status,but not with age,gender and WHO histological grade(P>0.05).IDH was negatively correlated with STAT1 in astrocytic tumors(r=-0.231,P<0.05).The results of univariate survival analysis showed that age,WHO histological grade,STAT1 positive expression and IDH mutation were significantly correlated with the prognosis of astrocytic tumor patients.The median survival time of STAT1 positive patients was higher than that of STAT1 negative patients(P<0.05),and the median survival time of IDH mutant patients was higher than that of wild type patients(P<0.05).If the expressions of IDH and STAT1 were considered together,the IDH(+)/ STAT1(+)group had the best prognosis,the IDH(-)/ STAT1(-)group had the worst prognosis,while IDH(+)/ STAT1(-)group and IDH(-)/ STAT1(+)group were between the two groups,but,the prognosis of IDH(-)/STAT1(+)group was better than that of IDH(+)/STAT1(-)group,and the difference was statistically significant.Multivariate survival analysis showed that STAT1 positive expression,IDH mutation,WHO histological grade and the combined expression of IDH-STAT1 are risk factors for the prognosis of patients with astrocytic tumors(P<0.05).2.IDH1/2 mutation was detected in 86 patients with WHO grade II～IV astrocytic tumors by Sanger sequencing,among which 37 cases had IDH mutation,and all of them were IDH1 R132 H mutation.The total mutation rate was43.0%(37/86),and no IDH2 mutations were found.Among them,there were 21 cases of WHO II grade,with a mutation rate of 60.0%(21/35).13 cases of WHO III grade with a mutation rate of 54.2%(13/24),and 3 cases of WHO IV grade with a mutation rate of 11.1%(3/27).The results of IDH1 IHC detection in 86 patients with WHO II～IV grade astrocytic tumors showed that 33 cases had IDH1 mutation.Among the 6specimens in which the two detection methods were inconsistent,5 case were negative by IHC,but positive by Sanger sequencing,and 1 case was positive by IHC,but negative by Sanger sequencing,with 93.0%(80/86)of the same test results,7.0%(6/86)There were differences in the detection results of the two methods;the results of the two detection methods had good consistency(Kappa=0.856),and the difference was not statistically significant(P>0.05).Conclusions:IDH as a potential tumor driving gene and STAT1 as a potential tumor suppressor gene,may all be involved in the occurrence and development of astrocytic tumors.IDH mutation and the decrease of STAT1 expression can predict the malignant degree of astrocytomas and evaluate the prognosis of patients to some extent.There is a negative correlation between IDH and STAT1 expression in astrocytic tumors,and IDH mutation may inhibit the expression of STAT1.