Deep learning-based multimodal pathogenomics integration for precision cancer prognosis.

[BACKGROUND] Recent studies have revealed valuable prognostic insights in haematoxylin and eosin (H&E)-stained histological sections and transcriptomic profiles, suggesting potential applications in machine learning. However, existing methods lack sufficient intra- and inter-modal interactions, and face challenges in clinical validation due to incomplete multimodal data.

[METHODS] We proposed PathoGems (PathoGenomics-based integrative survival prediction), a weakly-supervised, interpretable multimodal learning framework that integrates histology and genomic profiles for precise cancer prognosis prediction. To evaluate the robustness of PathoGems, we initially curated a dataset of 1965 cases across four cohorts from The Cancer Genome Atlas (TCGA), including breast, colorectal, glioblastoma, and esophageal cancers. For external validation, PathoGems was further evaluated on four independent cohorts, consisting of 76 breast cancer and 41 esophageal squamous cell carcinoma cases from Zhejiang Cancer Hospital, as well as 102 colorectal cancer and 58 glioblastoma cases from the Clinical Proteomic Tumor Analysis Consortium (CPTAC).

[RESULTS] PathoGems effectively stratified patients into favorable and unfavorable risk groups, revealing significant differences in histological patterns, genomic features, and overall survival (log-rank test,  < 0.05). Moreover, the model’s predictions are further supported by visualization and transcriptomic analysis, enhancing interpretability and reliability.

[CONCLUSIONS] By fusing histological and clinicogenomic multimodal models, PathoGems will provide a solid foundation for developing an innovative tool that aids clinicians in making informed decisions and selection personalized treatment strategies for cancer patients.

[SUPPLEMENTARY INFORMATION] The online version contains supplementary material available at 10.1186/s12967-026-07682-5.