Robust deep learning model for prognostic stratification of pancreatic ductal adenocarcinoma patients

Summary A major challenge for treating pancreatic ductal adenocarcinoma (PDAC) patients is the unpredictability of their prognoses due to high heterogeneity. We present Multi-Omics DEep Learning for Prognosis-correlated subtyping (MODEL-P) to identify PDAC subtypes and to predict prognoses of new patients. MODEL-P was trained on autoencoder integrated multi-omics of 146 PDAC patients together with their survival outcome. Using MODEL-P, we identified two PDAC subtypes with distinct survival outcomes (median survival 10.1 and 22.7 months respectively, log-rank p=1e-6), which correspond to DNA damage repair and immune response. We rigorously validated MODEL-P by stratifying patients in five independent datasets into these two survival groups and achieved significant survival difference which is superior to current practice and other subtyping schemas. We believe the subtype-specific signatures would facilitate PDAC pathogenesis discovery, and MODEL-P can provide clinicians the prognoses information in the treatment decision-making to better gauge the benefits versus the risks.