Linking MRI radiomics to transcriptomics-based radiosensitivity in lower-grade glioma: A radiogenomic framework

Abstract

Background: RSI is a transcriptomics-based biomarker associated with radiotherapy outcomes, but its clinical application is constrained by the requirement for tumor tissue and RNA sequencing. This study investigates whether MRI-derived radiomic features can reflect RSI-defined intrinsic radiosensitivity in lower-grade glioma. This addresses a critical gap arising from the limited availability of matched imaging and genomic data in routine clinical practice. Methods: MRI-derived radiomic features were extracted from FLAIR images of lower-grade glioma patients obtained from TCIA and matched with transcriptomic data from TCGA. A total of 107 patients with both MRI and RNA sequencing data were included in the radiogenomic analysis. Radiomic features were ranked using a Bordabased ensemble feature selection strategy. Five supervised machine-learning classifiers were trained to predict RSI-based radiosensitivity classification, and model interpretability was assessed using SHAP within radiogenomic framework. Results: Classification performance increased with feature number and stabilized at compact subset of 13 radiomic features. Logistic regression showed stable performance with an AUC of 0.82 (95 % CI: 0.71-0.93). SHAP analysis indicated that heterogeneity-related texture features were dominant contributors to model predictions, with many associated with the RR phenotype, while others were linked to the RS phenotype. Conclusion: An MRI-based radiomic signature enables non-invasive prediction of RSI-defined radiosensitivity in lower-grade glioma. Rather than offering an immediately deployable clinical tool, this study establishes a proofof-concept radiogenomic framework demonstrating that intrinsic radiosensitivity, traditionally assessed through invasive molecular assays, can be approximated using quantitative imaging features. These findings highlight the potential of imaging-based radiosensitivity assessment and provide a foundation for future radiogenomic investigations.