Prediction Of MGMT Promoter Methylation Status And Its Correlation With Ki-67 Expression In High-grade Gliomas Based On DKI And DTI

Objective:High grade glioma(HGG)is a kind of malignant brain tumor with highly invasive growth and high heterogeneity between and within tumor cells.Preoperative noninvasive evaluation of HGG biological behavior is very important for guiding the development of individualized treatment and evaluating prognosis.The purpose of this study is to study the MRI findings of DKI and DTI in HGG tumor parenchyma:(1)to explore the correlation between DKI and DTI related parameters and MGMT promoter methylation status;(2)to analyze the correlation between DKI and DTI related parameters and Ki-67 expression level;(3)to evaluate and compare the diagnostic efficacy of DKI and DTI in the above research results,so as to provide more accurate and reliable imaging information for preoperative design of individualized treatment plan and prognosis assessment for patients with high-grade glioma.Methods:This study prospectively collected 23 patients with high-grade glioma who underwent craniotomy and were confirmed by histopathological examination.All 23 patients received conventional MRI plain scan and enhanced scan,DKI and DTI scan before operation.Using the workstation of the equipment,DKI and DTI sequences were processed to obtain the following parameters: MK,RK and AK,ADC and FA.Three regions of interest(ROI)in HGG tumor parenchyma and normal brain parenchyma of HGG tumor parenchyma were manually depicted and measured by two senior radiologists,and the average value was taken and standardized.The tumor tissues after resection were:(1)the methylation status of MGMT promoter was detected by pyrosequencing;(2)the expression level of Ki-67 was detected by immunohistochemistry;(3)The correlation and predictive value of DKI and DTI parameters with MGMT promoter methylation and Ki-67 expression in HGG tumor parenchyma were analyzed and compared.Results:1.In this study,a total of 23 patients with high-grade glioma were collected,including 15 patients(65.2%)with MGMT promoter methylation and 8 patients(34.8%)with MGMT promoter non-methylation.There were 14 cases(60.9%)with high expression of Ki-67,and 9 cases(39.1%)with low expression of Ki-67.The mean age was 53.7±13.9 years(26-76 years).2.Correlation and predictive value of DKI and DTI parameters with MGMT promoter methylation in high-grade gliomas.(1)There were no significant differences in r MK value(0.89±0.12 vs0.92±0.10,P=0.503),r RK value(0.75±0.10 vs 0.78±0.05,P=0.508),r ADC value(1.05±0.12 vs 1.04±0.09,P=0.815)and r FA value(0.52±0.21 vs 0.41±0.23,P= 0.254)between tumor parenchyma MGMT promoter methylation group and non-methylated group.r AK value(1.00±0.15 vs 1.20±0.18,P=0.012)was statistically significant.(2)The rAK value was negatively correlated with the mutation status of MGMT promoter methylation(r=-0.490),and the AUC was 0.796,taking 1.12 as the the cut-off value,the sensitivity was 75%,the specificity was 86.7%,and 95%CI was0.586-1.000.3.Correlation and predictive value of DKI and DTI parameters with Ki-67 expression in high-grade gliomas.(1)The rMK value(0.95 ± 0.08 vs 0.82 ± 0.10,P = 0.004),rRK value(0.79± 0.05 vs 0.70 ± 0.10,P = 0.010),rAk value(1.17 ± 0.15 vs 0.91 ± 0.12,P <0.001)and rADC value(0.99 ± 0.09 vs 1.13 ± 0.09,P = 0.002)in the tumor parenchymal Ki-67 high expression group and Ki-67 low expression group were statistically significant,while the rFA value(0.52 ± 0.22 vs 0.42 ± 0.22,P =0.256)was not statistically significant.(2)rMK was positively correlated with the expression level of Ki-67(r=0.645),and the AUC was 0.881,taking 0.905 as the cut-off value,the sensitivity and specificity were 78.6% and 88.9%,95%CI: 0.744-1.000.rRK was positively correlated with the expression level of Ki-67(r=0.593),the AUC was 0.849,taking0.745 as the cut-off value,the sensitivity was 85.7%,the specificity was 55.6%,95%CI: 0.689-1.000.rAK was positively correlated with the expression level of Ki-67(r=0.808),and the AUC was 0.976,taking 0.975 as the cut-off value,the sensitivity was 100%,the specificity was 88.9%,95%CI: 0.921-1.000.r ADC value was negatively correlated with the expression level of Ki-67(r=-0.646),and AUC was0.881,taking 1.11 as the cut-off value,the sensitivity was 66.7%,the specificity was100%,95%CI: 0.732-1.000.Conclusions:1.rAK value of DKI quantitative parameter can provide reference for preoperative prediction of MGMT promoter methylation status in patients with high-grade glioma,and has a guiding role in the development of individualized treatment.2.rMK,rRK,rAK and rADC values of DKI and DTI quantitative parameters can reflect the expression level of Ki-67 in the tumor parenchyma of high-grade glioma,which can be used to measure tumor proliferation and contribute to the preoperative evaluation of tumor malignancy.Among them,rAK value has a higher diagnostic value.3.Compared with DTI,DKI has greater advantages in comprehensively predicting the methylation status of MGMT promoter and the expression level of Ki-67 in high-grade glioma.