BACKGROUND: The objective of this comprehensive pan-cancer study is to evaluate the potential of deep learning (DL) for molecular profiling of multi-omic biomarkers directly from hematoxylin and eosin (H&E)-stained whole slide images.

METHODS: A total of 12,093 DL models predicting 4031 multi-omic biomarkers across 32 cancer types were trained and validated. The study included a broad range of genetic, transcriptomic, and proteomic biomarkers, as well as established prognostic markers, molecular subtypes, and clinical outcomes.

RESULTS: Here we show that 50% of the models achieve an area under the curve (AUC) of 0.644 or higher. The observed AUC for 25% of the models is at least 0.719 and exceeds 0.834 for the top 5%. Molecular profiling with image-based histomorphological features is generally considered feasible for most of the investigated biomarkers and across different cancer types. The performance appears to be independent of tumor purity, sample size, and class ratio (prevalence), suggesting a degree of inherent predictability in histomorphology.

CONCLUSIONS: The results demonstrate that DL holds promise to predict a wide range of biomarkers across the omics spectrum using only H&E-stained histological slides of solid tumors. This paves the way for accelerating diagnosis and developing more precise treatments for cancer patients.