Comprehensive quantitative radiogenomic evaluation reveals novel radiomic subtypes with distinct immune pattern in glioma

Accurate classification of gliomas is critical to the selection of immunotherapy, and MRI contains a large number of radiomic features that may suggest some prognostic relevant signals. We aimed to predict new subtypes of gliomas using radiomic features and characterize their survival, immune, genomic profiles and drug response. We initially obtained 341 images of 36 patients from the CPTAC dataset for the development of deep learning models. Further 1812 images of 111 patients from TCGA_GBM and 152 images of 53 patients from TCGA_LGG were collected for testing and validation. A deep learning method based on Mask R-CNN was developed to identify new subtypes of glioma patients and compare the survival status, immune infiltration patterns, genomic signatures, specific drugs, and predictive models of different subtypes. 200 glioma patients (mean age, 33 years ± 19 [standard deviation]) were enrolled. The accuracy of the deep learning model for identifying tumor regions achieved 88.3% (98/ 111) in the test set and 83% (44/53) in the validation set. The sample was divided into two subtypes based on radiomic features showed different prognostic outcomes (hazard ratio, 2.70). According to the results of the immune infiltration analysis, the subtype with a poorer prognosis was defined as the immunosilencing radiomic (ISR) subtype (n=43), and the other subtype was the immunoactivated radiomic (IAR) subtype (n=53). Subtype-specific genomic signatures distinguished celllines into ISR celllines (n=9) and control celllines (n=13), and identified eight ISR-specific drugs, four of which were validated by the OCTAD database. Three machine learning-based classifiers showed that radiomic and genomic co-features better predicted the radiomic subtypes of gliomas. These findings provide insights into how radiogenomic could identify specific subtypes that predict prognosis, immune and drug sensitivity in a non-invasive manner.