| Objective: Glioma is the most common primary brain tumor,and its early qualitative diagnosis and grading are invaluable for the choice of surgical approach and prognosis of patients.Gliomas are genotyped on the basis of molecular pathology tests introduced by the World Health Organization(WHO)up till the present moment.A large number of biomarkers,containing isocitrate dehydrogenase(IDH)mutation status,06-methylguanine-DNA-methyltransferase(MGMT)promoter methylation status,telomerase reverse transcriptase(TERT)promoter type and co-deletion of chromosome arm 1p/19 q,provide guidance for the prognosis and postoperative treatment of glioma.Human brain tumor metabolites can be checked and measured by the Magnetic resonance spectroscopy(MRS),which is regarded as a major imaging modality to determine the type and grading of most brain tumors.Clarification of glioma metabolic differences may provide assistance in preoperative grading of gliomas,prediction of genotyping and the development of surgical plans.The aim of this research is using multivoxel MRS to establish the amount of metabolites in solid components of tumor,peritumoral and contralateral normal white matter region,to analyze the differences and correlation between metabolites in different regions and the common clinical genotyping and immunohistochemical markers of gliomas,in order to make clear if there are obvious global changes of brain metabolites in different gene types of gliomas.Futheremore,we hope to provide imaging basis for clinical diagnosis and prognosis of gliomas.Methods: We collected the clinical information of 79 patients with glioma(including complete preoperative MRS imaging data,molecular pathology data,follow-up data),and compared the different types of molecular pathology indicators with the metabolites measured by MRS in the central region of the tumor,the surrounding region of the tumor and the contralateral normal white matter region through Mann-Whitney U test and rank sum test,and performed immunohistochemical staining on the glioma tissue samples obtained during the operation.Spearman method was used to analyze the correlation between the expression level of Ki-67 and P53 in tumor tissue and brain tissue metabolites.According to the follow-up results of patients(including survival time,recurrence time,whether to carry out radiotherapy and chemotherapy),the Kaplan-Meier survival analysis and COX single factor and multiple factor analysis were used to build a prognosis model to study the prognosis of glioma patients with different gene groups.In this study,P<0.05 was used as a statistically significant indicator.Results: In solid components of tumor,Cho/NAA and Cho/Cr ratios were positively correlated with the grade of tumor.The difference of Cho/NAA and Cho/Cr ratio in different IDH1 types of glioma was statistically significant(Z value was-1.848 and-2.234,respectively,P<0.05);There were no significant differences in the ratios of Cho/NAA,Cho/Cr and NAA/Cr between MGMT promoter methylated and unmethylated glioma,TERT gene mutant and unmutated,and 1p/19 q deletion types(P>0.05);In addition,Cho/NAA and Cho/Cr were positively correlated with the expression of Ki-67,with correlation coefficients of 0.286 and 0.352,respectively(P<0.05).Cho/Cr was moderately positively correlated with the expression of p53,with correlation coefficient of 0.424,and the difference was statistically significant(P=0.012).However,Cho/NAA may not be positively correlated with the expression of p53 in the central region of the tumor(P=0.051).In peritumoral region,there was a significant difference in the ratio of Cho/NAA between IDH mutant and wild-type glioma(Z=-2.719,P<0.01),the ratio of Cho/Cr between methylated and unmethylated type of MGMT promoter(Z=-2.942,P<0.01),and the ratio of Cho/Cr,Cho/NAA and NAA/Cr among different TERT gene types was not statistically significant(P>0.05),The difference of Cho/Cr in the four 1p/19 q molecular subtypes was statistically significant(P<0.05).The difference of NAA/Cr ratio with no statistically significant(P=0.053)due to the small sample size.The ratio of Cho/Cr,Cho/NAA and NAA/Cr had no significant correlation with the expression of Ki-67 in the peritumoral region(P>0.05),while the ratio of Cho/NAA was positively correlated with the expression of p53,with a correlation coefficient of 0.317,However,NAA/Cr was negatively correlated with the expression of p53,and the correlation coefficient was-0.498,which was statistically significant(P<0.05).The Cho/NAA ratio in the peritumoral region was significantly different among the five molecular subtypes of glioma(P<0.05).In the normal white matter area on the opposite side of the tumor,the differences between the ratio of Cho/NAA,Cho/Cr and NAA/Cr and the WHO grade of glioma with no statistical significance,IDH gene type,MGMT promoter methylation status,TERT gene mutation type and 1p/19 q chromosome deletion type(P>0.05).According to the results of multivariate analysis,WHO grade,whether to undergo radiotherapy and chemotherapy after operation,Cho/Cr and MGMT methylation status are the survival related factors of patients,which grade 4glioma is a risk factor for survival compared with grade 2 glioma {HR: 7.685(2.545-16.856),P<0.01},and postoperative radiotherapy and chemotherapy is a protective factor for survival of patients {HR: 0.110(0.017-0.716),P<0.05}.The ratio of Cho/Cr in tumor area is a risk factor for survival of patients {HR:3.396(1.133-9.098),P<0.05},and the methylation status of MGMT is a protective factor for survival of glioma {HR: 0.274(0.086-0.873),P<0.05}.Finally,the survival curves of patients with different risk scores were constructed according to the indicators of WHO4 grade,no radiotherapy and chemotherapy after operation,Cho/Cr>2.195 and MGMT unmethylation.The results displayed the mean survival time of low-risk group,medium and high-risk group was 46.5,36.2 and 9.3 months respectively,and the difference was statistically significant according to the log-rank test(P<0.05).Conclusion: The status of molecular pathology genes(IDH,MGMT,1p/19q)of glioma may be related to the distribution of brain metabolites.The magnetic resonance spectroscopy can further display the differential changes of Cho,NAA,Cr,and preliminarily find that the multiple parameters of MRS are related to the proliferation of glioma and tumor prognosis. |
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