Self-supervised learning reveals clinically relevant histomorphological patterns for therapeutic strategies in colon cancer.

Journal: Nature communications
PMID:

Abstract

Self-supervised learning (SSL) automates the extraction and interpretation of histopathology features on unannotated hematoxylin-eosin-stained whole slide images (WSIs). We train an SSL Barlow Twins encoder on 435 colon adenocarcinoma WSIs from The Cancer Genome Atlas to extract features from small image patches (tiles). Leiden community detection groups tiles into histomorphological phenotype clusters (HPCs). HPC reproducibility and predictive ability for overall survival are confirmed in an independent clinical trial (N = 1213 WSIs). This unbiased atlas results in 47 HPCs displaying unique and shared clinically significant histomorphological traits, highlighting tissue type, quantity, and architecture, especially in the context of tumor stroma. Through in-depth analyses of these HPCs, including immune landscape and gene set enrichment analyses, and associations to clinical outcomes, we shine light on the factors influencing survival and responses to treatments of standard adjuvant chemotherapy and experimental therapies. Further exploration of HPCs may unveil additional insights and aid decision-making and personalized treatments for colon cancer patients.

Authors

  • Bojing Liu
    Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
  • Meaghan Polack
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
  • Nicolas Coudray
    Applied Bioinformatics Laboratories, NYU Grossman School of Medicine, New York, NY, USA. nicolas.coudray@nyulangone.org.
  • Adalberto Claudio Quiros
    School of Computing Science, University of Glasgow, Glasgow, Scotland, UK.
  • Theodore Sakellaropoulos
    Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA.
  • Hortense Le
    Department of Medicine, Division of Precision Medicine, NYU Grossman School of Medicine, New York, USA.
  • Afreen Karimkhan
    Department of Pathology, NYU Grossman School of Medicine, New York, NY, USA.
  • Augustinus S L P Crobach
    Department of Pathology, Leiden University Medical Center, Leiden, The Netherlands.
  • J Han J M van Krieken
    Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands.
  • Ke Yuan
    Department of Biomedical Engineering, The Chinese University of Hong Kong, Shatin, N.T., Hong Kong.
  • Rob A E M Tollenaar
    Department of Surgery, Leiden University Medical Center, Leiden, the Netherlands.
  • Wilma E Mesker
    Department of Surgery, Leiden University Medical Center, Leiden, The Netherlands.
  • Aristotelis Tsirigos
    Department of Pathology, NYU School of Medicine, New York, NY 10016, USA; Laura and Isaac Perlmutter Cancer Center, NYU School of Medicine, New York, NY 10016, USA; Applied Bioinformatics Laboratories, NYU School of Medicine, New York, NY 10016, USA. Electronic address: aristotelis.tsirigos@nyulangone.org.