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

Summary: A major challenge for treating patients with pancreatic ductal adenocarcinoma (PDAC) 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...

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Autores principales: Jie Ju, Leonoor V. Wismans, Dana A.M. Mustafa, Marcel J.T. Reinders, Casper H.J. van Eijck, Andrew P. Stubbs, Yunlei Li
Formato: article
Lenguaje:EN
Publicado: Elsevier 2021
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Acceso en línea:https://doaj.org/article/bac116467aa74791ac6eb847e3be8b38
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Sumario:Summary: A major challenge for treating patients with pancreatic ductal adenocarcinoma (PDAC) 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 patients with PDAC 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 = 1 × 10−6), 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.