The Significance Of Multi-gene Target Detection In The Treatment Of Glioma

Objective: To explore the significance of multigene target detection(including MGMT promoter methylation,IDH1 gene mutation,1p/19 q codeletion)in the treatment of glioma.Methods: Select 174 cases admitted in quondam PLA Shenyang Military General Hospital from May 2012 to May 2017.All patients undergo surgical treatment and are confirmed by postoperative pathology as glioma.Tumor specimen and blood sample are collected and the multigene target detection is performed.All patients' tumors are totally resected with microscopy technique.The MGMT promoter methylation and IDH1 gene mutation are detected respectively in the way of pyrosequencing and PCR sequencing analysis.Use fluorescence PCR capillary electrophoresis to detect 1p/19 q codeletion.Meanwhile,we collect clinical data and analyse the distribution differences of above genetic sites on different clinical charactorsincluding age,gender,KPS score,pathological grade,p53 expression and Ki67 expression.Then,we investigate the correlation between the above genetic targets by Chi-square test and Spearman correlation test based on SPSS 22.0.We accurately record patients' overall survival(OS)in a variety of ways including outpatients review,wechat and telephone interview.OS comparation in different genotypes and groups are performed by drawing survival curves with Kaplan-Meier method.In our study,the status of ATRX gene,BRAF gene,EGFR gene,PIK3 CA gene and TP53 gene are also tested in some patients.Especially,the detection of TERT gene is carried out according to the WHO Classification of Tumors of The Central Nervous Systerm.This paper summarizes our experience and explores the significance of multigene target detection in the treatment of glioma.Results: 1.There are 88 cases(50.57%)with MGMT promoter methylation found among all patients.The distribution difference of MGMT promoter methylation has no statistical significance on age(P=0.636),gender(P=0.642),KPS score(P=0.339),pathological grade(P=0.168)and Ki67 expression(P=0.293)except for P53 expression(P=0.022).2.In our study,there are 32 cases(18.39%)with IDH1 gene mutation.After statistic analysis,we find that IDH1 gene mutation is only associated with age(P=0.009),while it has no relationship with gender(P=0.718),KPS score(P=0.143),pathological grade(P=0.060),Ki67 expression(P=0.100)and P53 expression(P=0.672).3.According to the statistical result,1p/19 q codeletion is 27.01%(47/174).we find significant statistical difference existed between 1p/19 q codeletion and P53expression(P=0.045),Ki67 expression(P=0.015).However,the differences are not found when compared with age(P=0.314),gender(P=0.097),KPS score(P=0.401)and pathological grade(P=0.182).4.When compared the correlation and distribution difference among the target sites,we find positive correlation between MGMT gene promoter methylation and1p/19 q codeletion(r = 0.187,P = 0.014)and IDH1 gene mutation(r = 0.113,P = 0.135).At the same time,positive correlation(r=0.179,P=0.018)also exists between 1p/19 q codeletion and IDH1 gene mutation.However,the relationship in these genetic targets is not significant.To the distribution of above genetic sites,there is statistical difference between MGMT promoter methylation and 1p/19 q correlation.The difference also exists between 1p/19 q correlation and IDH1 gene mutation.5.All patients are divided into three groups according to pathological classification,that is,high-grade group,low-rade group and overall group.and the survival curve of overall survival is made out.For patients with MGMT gene promoter methylation,both in overall group and in high-level group have a longer overall survival and better prognosis when compared with non-methylation patients.Within overall group and high-level group,patients with IDH1 gene mutation and 1p/19 q codeletion had better prognosis,while those genetic changes in low-grade group fail to reveal a statistically significance on overall survival.Conclusion: MGMT gene promoter methylation has relation with P53 expression,while age has an effect on the distribution of IDH1 gene mutation.The distribution of1p/19 q codeletion has statistic difference on Ki67 and P53 expression.There are positive correlations within MGMT gene promoter methylation,IDH1 gene mutation and 1p/19 q codeletion,but the correlations are not significant.Patients with MGMT gene promoter methylation have a longer overall survival time and better prognosis when compared with the non-methylation.High level glioma with IDH1 gene mutation and 1p/19 q codeletion has a longer overall survival time.With the detection of multi-gene target,we can accurately predict the prognosis and the sensitivity to radiotherapy and chemotherapy.At the same time,multigene target detection is a favorable complement to pathological diagnosis and accurate medical treatment can be truly achieved during the patients' diagnosis and treatment.