The Relationship Of Magnetic Resonance Spectroscopy Parameters And Expression Of MGMT In Glioblastoma

Background and objectiveGliomas is the most common malignant tumors of the central nervous system(CNS),Maximum safe resection and adjuvant chemotherapy is the standard treatment,but the overall prognosis of the patients has not been improved significantly,especially in Glioblastoma(GBM)with 14 months of medium survival.06-methylguanine-DNAmethyhransferase(MGMT)promoter methylation events in epigenetics are important for predicting prognosis and chemotherapeutic sensitivity of GBM.The changes of gene expression involved in gliomas are often associated with DNA methylation and epigenetic changes in chromosomes: MGMT is a DNA-repaired enzyme that protects cells from carcinogens by stripping alkyl from DNA,in some malignant gliomas,excessive methylation of the DNA promoter causes MGMT silence,which makes the tumor respond well to Mozuoe.The GBM with MGMT promoter methylation has a better clinical process and prognosis than another group.Imaging genomics can make use of the advantages of modern imaging to predict the gene phenotype of glioma,especially with the rapid development of magnetic resonance technology,structural imaging and functional imaging can provide tumor growth and metabolic information from different angles,thus laying a foundation for microcosmic study of GBM molecular phenotype.The study of relationship between magnetic resonance imaging(MRI)and methylation of MGMT promoter was helpful to predict tumor molecular phenotype and evaluate prognosis and adjuvant therapy before operation or tumor puncture.Magnetic resonance spectroscopy(MRS)can continuously observe the concentration of a variety of metabolites that play an important role in neurobiology.The study on the relationship between 3D-MRS and GBM MMT methylation provides effective information for precise therapy,but there is no clear conclusion whether MRS quantitative parameters are correlated with MGMT methylation status.In this study,the relationship between 3D-MRS parameters and MGMT methylation state and its predictive value were analyzed.Methods and materialsCollected 35 cases of Glioblastoma(Pathological confirmation)from June 2016 to December 2016 in the glioma group of Huashan Hospital affiliated to Fudan University.Compliance with inclusion criteria:(1)Histopathology confirmed that the original GBM,tumor that located on the curtain,no more lesions;Determination of MGMT methylation status by molecular pathology.(2)GBM patients underwent no radiotherapy and chemotherapy before imaging examination.(3)Patient informed and sign informed consent,cooperate with relevant examination and treatment.(4)MRI sequence scan before operation and original data retained intact.(5)The baseline of MRS is stable and high parameter reliability.Statistical methodsAll data are statistically processed using SPSS 22.0 software,and the drawing tool uses GraphPad Prism 7.0.In this study,MGMT and non-methylated magnetic resonance spectra parameters of Cho/NAA、Cho/Cr、NAA/Cr、 Cho、NAA、Lac and Lip were analyzed statistically:(1)Non-parametric test(Kruskal-Wallis test),with statistically significant differences in parameters.(2)Correlation test(Spearman correlation analysis),correlation test for parameters with statistical differences and calculate correlation coefficient.(3)Assessment of projected values,the area,threshold,sensitivity and specificity under the ROC curve are obtained by evaluating the predictive value.The difference was set to P<0.05.Results1.This study included 35 cases of Glioblastoma,19 of which were male(about54%)and 16 of which were female(about 46 %): MGMT methylation group(14 cases),methylation group(about 40 %),male 9 cases,female 5 cases,average age(53.24+12.36years);21 cases of MGMT Non-methylation with 10 males and 11 females with average age(52.38+14.52 years).2.The results of the non-parametric tests showed no statistical differences between the two groups in the values of Cho/NAA(4.41±0.51 vs 5.19±0.45,P=0.189),Cho/Cr(2.69±0.29 vs 2.47±0.20,P=0.691),NAA/Cr(0.74±0.07 vs 0.92±0.12,P=0.526),Cho(3.17±0.46 vs 4.38±0.65,P=0.164,P=0.164),NAA(1.12±0.17 vs 1.49±0.21,P=0.313),The values of Lac(1.24+0.13 vs 0.39+0.08)and Lip(1.16+0.14 vs 0.41+0.10)of the non-methylation group were significantly higher than those of the methylation groupwith statistical differences.3.Lac was negatively correlated with MGMT methylation(r=-0.67),the area under ROC curve was 0.849,with 0.65 as the threshold,sensitivity and specificity being88.5 % and 81.1 % respectively.Lip and MGMT methylation was negatively correlated(r=-0.543),the area under ROC curve was 0.82,with 0.54 as the threshold,sensitivity and specificity being 73.9 % and 78.1 % respectively.Conclusion1.3D-MRS can collect more spectral information of Glioblastoma,and it is helpful to find the difference between MGMT methylation and non-methylation,Metabolites Lac and Lip were the most significant differences.2.3D-MRS is helpful to find out the difference of metabolism between MGMT methylation and non-methylation.Lac、Lip and MGMT are negatively correlated.MRS data can be used to evaluate the tumor environment,especially the metabolic difference.3.The Lac and Lip spectra collected by 3D-MRS can be used to predict the MGMT methylation status of GBM,Lac is more effective than Lip in predicting MGMT methylation status,assisting surgical planning and prognostic judgment.The spectrum parameters of GBM were significantly correlated with the methylation of MGMT,which was helpful to predict the methylation status of MGMT before operation,to infer the metabolism in tumor,and to provide an effective basis for the evaluation of operation and prognosis.