An MRI Radiogenomic Signature to Characterize the Transcriptional Heterogeneity Associated with Prognosis and Biological Functions in Glioblastoma.

Abstract

Background: The study sought to establish a radiogenomic signature to evaluate the transcriptional heterogeneity that reflects the prognosis and tumour-related biological functions of patients with glioblastoma.

Methods: Transcriptional subclones were identified via fully unsupervised deconvolution of RNA sequencing. A genomic prognostic risk score was developed from transcriptional subclone proportions in the development dataset (n = 532) and independently verified in the testing dataset (n = 225). Multimodal magnetic resonance imaging (MRI) analysis involved feature extraction from three distinct anatomical regions across four imaging sequences. Key features were selected to construct a radiogenomic signature predictive of the genomic risk score in the radiogenomic dataset (n = 99), with subsequent survival analysis conducted in the image testing dataset (n = 233).

Results: A total of 8 transcriptional subclones were identified, of which the metabolic pathway subclone and spinocerebellar ataxia subclone were independent risk factors for overall survival. The genomic risk score effectively differentiated patient subgroups with divergent survival outcomes in both development (p < 0.001) and testing datasets (p = 0.0003). Nineteen radiomic features were selected to construct a radiogenomic signature, with these features being linked to hallmark cancer pathways and the malignant behaviours of cancer cells. The radiogenomic signature predicted overall survival in the image testing dataset (hazard ratios (HR) = 1.67, p = 0.011).

Conclusions: A prognostic radiogenomic signature was established and verified to characterize transcriptional subclones with underlying biological functions in glioblastoma.