Biological underpinnings of radiomic magnetic resonance imaging phenotypes for risk stratification in IDH wild-type glioblastoma

To develop and validate a conventional MRI-based radiomic model for predicting prognosis in patients with IDH wild-type glioblastoma (GBM) and reveal the biological underpinning of the radiomic phenotypes. A total of 801 adult patients (training set, N = 471; internal validation set, N = 239; external validation set, N = 91) diagnosed with IDH wild-type GBM were included. A 20-feature radiomic risk score (Radscore) was built for overall survival (OS) prediction by univariate prognostic analysis and least absolute shrinkage and selection operator (LASSO) Cox regression in the training set. GSEA and WGCNA were applied to identify the intersectional pathways underlying the prognostic radiomic features in a radiogenomic analysis set with paired MRI and RNA-seq data (N = 132). The biological meaning of the conventional MRI sequences was revealed using a Mantel test. Radscore was demonstrated to be an independent prognostic factor (P < 0.001). Incorporating the Radscore into a clinical model resulted in a radiomic-clinical nomogram predicting survival better than either the Radscore model or the clinical model alone, with better calibration and classification accuracy (a total net reclassification improvement of 0.403, P < 0.001). Three pathway categories (proliferation, DNA damage response, and immune response) were significantly correlated with the prognostic radiomic phenotypes. Our findings indicated that the prognostic radiomic phenotypes derived from conventional MRI are driven by distinct pathways involved in proliferation, DNA damage response, and immunity of IDH wild-type GBM.