Regression-based Deep-Learning predicts molecular biomarkers from pathology slides.

Journal: Nature communications
PMID:

Abstract

Deep Learning (DL) can predict biomarkers from cancer histopathology. Several clinically approved applications use this technology. Most approaches, however, predict categorical labels, whereas biomarkers are often continuous measurements. We hypothesize that regression-based DL outperforms classification-based DL. Therefore, we develop and evaluate a self-supervised attention-based weakly supervised regression method that predicts continuous biomarkers directly from 11,671 images of patients across nine cancer types. We test our method for multiple clinically and biologically relevant biomarkers: homologous recombination deficiency score, a clinically used pan-cancer biomarker, as well as markers of key biological processes in the tumor microenvironment. Using regression significantly enhances the accuracy of biomarker prediction, while also improving the predictions' correspondence to regions of known clinical relevance over classification. In a large cohort of colorectal cancer patients, regression-based prediction scores provide a higher prognostic value than classification-based scores. Our open-source regression approach offers a promising alternative for continuous biomarker analysis in computational pathology.

Authors

  • Omar S M El Nahhas
    Else Kroener Fresenius Center for Digital Health, Technical University Dresden, Dresden, Germany.
  • Chiara M L Loeffler
    Department of Medicine 1, University Hospital Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
  • Zunamys I Carrero
    Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden, Dresden, Germany.
  • Marko van Treeck
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Fiona R Kolbinger
    Department of Visceral, Thoracic and Vascular Surgery, Faculty of Medicine and University Hospital Carl Gustav Carus, TUD Dresden University of Technology, Dresden, Germany; Weldon School of Biomedical Engineering, Purdue University, West Lafayette, Indiana.
  • Katherine J Hewitt
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.
  • Hannah S Muti
    Else Kroener Fresenius Center for Digital Health, Technical University Dresden, Dresden, Germany; Department of Visceral, Thoracic and Vascular Surgery, University Hospital Carl Gustav Carus Dresden, Dresden, Germany.
  • Mara Graziani
  • Qinghe Zeng
    Centre d'Histologie, d'Imagerie et de Cytométrie (CHIC), Centre de Recherche des Cordeliers, INSERM, Sorbonne Université, Université de Paris, Paris, France.
  • Julien Calderaro
    Department of Pathology, Henri Mondor University Hospital, Créteil, France.
  • Nadina Ortiz-Brüchle
    Institute of Pathology, University Hospital RWTH Aachen, Aachen, Germany.
  • Tanwei Yuan
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Michael Hoffmeister
    Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, Germany.
  • Hermann Brenner
    German Cancer Consortium (DKTK), Heidelberg, Germany.
  • Alexander Brobeil
    Institute of Pathology, University of Heidelberg, Heidelberg, Germany; Tissue Bank of the National Center for Tumor Diseases (NCT), Heidelberg, Germany.
  • Jorge S Reis-Filho
    Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
  • Jakob Nikolas Kather
    Department of Medicine III, University Hospital RWTH Aachen, Aachen, Germany.