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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
Lower-Grade Gliomas: Predicting DNA Methylation Subtyping and its Consequences on Survival with MR Features
Hongdan Zhang1, Li Xu2, Zhiping Zhong2
1Department of Radiotherapy, Cancer Center, Guangdong Provincial People's Hospital (Guangdong Academy of Medical Sciences), Guangzhou 510080, People's Republic of China.
Rationale And Objectives:
To explore associations between MR imaging features, DNA methylation subtyping, and survival in lower-grade gliomas (LGG).
Materials And Methods:
The MR data from 170 patients generated with the Cancer Imaging Archive were reviewed. The correlation was evaluated by Fisher's Exact Test, Pearson Chi-Square and binary regression analysis. Survival analysis was conducted by using time-dependent ROC analysis and the Kaplan-Meier method (the worst prognosis subgroup).
Results:
Identified were 9 (5.3%) M1-subtype, 18 (10.6%) M2-subtype, 48 (28.2%) M3-subtype, 31 (18.2%) M4-subtype and 64 (37.6%) M5-subtype. Patients with M4-subtype had the shortest median OS (49.3 vs. 28.4) months(p < 0.05). The time-dependent ROC for the M4-subtype was 0.83 (95% confidence interval 0.72-0.95) for survival at 12 months, 0.82 (95% confidence interval 0.70-0.94) for survival at 24 months, and 0.74 (95% confidence interval 0.62-0.86) for survival at 36 months. After uni- and multivariate analysis, a nomogram was built based on proportion contrast-enhanced (CE) tumor, extranodular growth, volume_cutoff_median, and location. For the prediction of M4-subtype, the nomogram showed good discrimination, with an area under the curve (AUC) of 0.886 (95% CI: 0.820-952) and was well calibrated. On multivariate logistic regression analysis, volume ≥60cm3 (OR: 0.200; p < 0.001; 95%CI: 0.048-0.834) was associated with M1-subtype (AUC: 0.690). Hemorrhage (OR: 5.443; p = 0.002; 95%CI: 1.844-16.069) and volume > median (OR: 3.256; p = 0.05; 95%CI: 0.992-10.686) were associated with M2-subtype (AUC: 0.733). Proportion CE tumor<=5% (OR: 3.968; P=0.002; 95%CI: 1.634-9.635) was associated with M3-subtype (AUC: 0.632). Poorly-defined (OR: 2.258; p = 0.05; 95%CI: 1.000-5.101) and volume > median (OR: 2.447; p = 0.01; 95%CI: 1.244-4.813) were associated with M5-subtype (AUC: 0.645). Decision curve analysis indicated predictions for all models were clinically useful.
Conclusion:
This preliminary radiogenomics analysis of lower-grade gliomas demonstrated associations between MR features and DNA methylation subtyping. The shortest survival was observed in patients with M4-subtype. And we have constructed nomogram that enables more accurate predictions of M4-subtype.

