Radiomics-Based Gradient Boosting Model on Contrast-Enhanced MRI for Non-Invasive Prediction of Epidermal growth factor receptor Expression and Therapeutic Response to EGFR-Targeted antibody-drug conjugates in High-Grade Glioma Organoid Models

Abstract Background: Epidermal growth factor (EGF) and its receptor EGF(EGFR) play crucial roles in glioblastoma (GBM) prognosis. However, non-invasive assessment of their expression remains challenging. Radiomics offers potential for decoding tumor biology from imaging data. This study aimed to develop a radiomics-based model to predict EGFR expression, explore their associations with the tumor microenvironment and therapy sensitivity of EGFR-Targeted antibody-drug conjugates (EGFR-ADCs) in GBM. Methods: We extracted radiomic features from contrast-enhanced MRI of 298 GBM patients from The Cancer Imaging Archive (TCIA) and matched them with RNA-seq data from The Cancer Genome Atlas (TCGA). Feature selection was performed using minimum redundancy maximum relevance (mRMR) and recursive feature elimination (RFE). Machine learning models were built to predict EGF/EGFR expression. Radiogenomic associations were validated by immune cell infiltration analysis. Patient-Derived Tumor-Like Cell Clusters (PTC) were used to compare the antitumor efficacy of EGFR- ADCs and temozolomide. Results: Elevated EGF/EGFR expression correlated with poor prognosis and increased infiltration of M2 macrophages, regulatory T cells, and CD4⁺ memory T cells. Pathway analysis demonstrated significant enrichment of the mechanistic target of rapamycin (mTOR) and Mitogen-Activated Protein Kinase (MAPK) signaling cascades. Radiomics-based prediction models achieved robust performance (AUC > 0.85) in stratifying EGFR expression status. In EGFR-positive tumor tissues, EGFR-ADCs exerted antitumor efficacy similar to that of temozolomide. Conclusions: EGF/EGFR expression is associated with immunosuppressive microenvironments and adverse outcomes in Highgrade gliomas (HGG). Radiomics enables noninvasive EGFR profiling, and EGFR-ADCs demonstrate promising therapeutic efficacy. These findings provide new insights into radiogenomic stratification and targeted therapy in GBM.