Prognostic Value Of A Risk-score Model Based On Integrated Molecular-pathology Features For High-grade Gliomas

Background and Objective: High-grade gliomas(HGGs)are the most common brain malignancies,accounting for more than half of primary central nervous system malignancies.The prognosis of patients with the same pathological grade is still quite different.The purpose of this study is to establish a molecular pathology risk score model by investigating the association between molecular-pathology features and prognosis,and construct a nomogram of HGGs for the survival rate prediction combined with clinical factors.Methods: A retrospective cohort study was conducted in HGGs patients treated with postoperative intensity modulated radiotherapy.All patients were diagnosed with primary HGGs pathologically and received surgery and postoperative intensity modulated radiotherapy.The detection about the mutation of isocitrate dehydrogenase(IDH),telomerase reverse transcriptase(TERT),and V600 E mutation of v-Raf murine sarcoma viral oncogene homolog B1 gene(BRAF),the promoter methylation level of O6-methylguanine DNA methyltransferase(MGMT),the co-deletion status of chromosome 1p/19 q,the expression level of tumor protein(P53),and proliferation index(ki-67)were performed.Forward and backward stepwise regression analyses was employed to select molecular pathology features and develop a molecular pathology risk score model.By combining the molecular pathology risk score and clinical factors,a nomogram was constructed and showed with the web version in order to increase its practicability and maneuverability.Its performance was evaluated by Harrell’s concordance index,time-dependent receiver operating characteristic(ROC)curves,and calibration curves.Results: A total of 91 patients with HGGs who received postoperative intensity modulated radiotherapy were included in this study.The follow-up rate was 99.0%and the median follow-up time was 21.1months.A total of 31 patients(34.1%)died.The prevalence of MGMT promoter methylation,P53>40%,IDH1/2 gene mutation,TERT gene mutation,BRAF V600 E gene mutation and chromosome 1p/19 q co-deletion were 56.0%,45.1%,29.7%,20.9%,12.1% and 3.3%,respectively.After forward and backward stepwise regression analyses,four molecular pathology features(IDH1/2,TERT,P53,ki-67)were used in the molecular pathology risk score model based on a smaller Akaike information criterion value.Univariate Cox regression analysis showed that molecular pathology risk score model was a prognostic factor for HGGs(HR = 2.718,95% CI:1.579-4.680).The area under the ROC curve(AUC)and C-index of the molecular pathology risk score model for predicting 2-year survival rate of HGGs patients were 0.819,and 0.722,respectively.Multivariate Cox regression analysis was performed with age,pathological grade,simultaneous radiotherapy and chemotherapy,adjuvant chemotherapy and molecular pathological risk score model.The results showed that molecular pathological risk score(HR=2.098,P=0.035)and WHO grade(HR=6.079,P=0.024)were independent prognostic factors for HGGs.A nomogram was constructed based on the results of multivariate Cox analysis.The AUC of 1-year and 2-year time-dependent ROC curves of the nomogram was 0.735,and 0.868,respectively.Conclusion: This study developed a molecular pathology risk score model based on IDH1/2,TERT,P53 and ki-67,achieved the integrated analysis of molecular-pathology features of HGGs.This study provided a novel view of HGGs risk stratification,and a reference for individualized treatment.