Machine Learning-Based Multimodal Radiomics and Transcriptomics Models for Predicting Radiotherapy Sensitivity and Prognosis in Esophageal Cancer

Radiotherapy plays a critical role in treating esophageal cancer, but individual responses vary significantly, impacting patient outcomes. This study integrates machine learning-driven multimodal radiomics and transcriptomics to develop predictive models for radiotherapy sensitivity and prognosis in esophageal cancer. We applied the SEResNet101 deep learning model to imaging and transcriptomic data from the UCSC Xena and TCGA databases, identifying prognosis-associated genes such as STUB1, PEX12, and HEXIM2. Using Lasso regression and Cox analysis, we constructed a prognostic risk model that accurately stratifies patients based on survival probability. Notably, STUB1, an E3 ubiquitin ligase, enhances radiotherapy sensitivity by promoting the ubiquitination and degradation of SRC, a key oncogenic protein. In vitro and in vivo experiments confirmed that STUB1 overexpression or SRC silencing significantly improves radiotherapy response in esophageal cancer models. These findings highlight the predictive power of multimodal data integration for individualized radiotherapy planning and underscore STUB1 as a promising therapeutic target for enhancing radiotherapy efficacy in esophageal cancer.