Nature Communications (Dec 2023)
Deep learning-based phenotyping reclassifies combined hepatocellular-cholangiocarcinoma
- Julien Calderaro,
- Narmin Ghaffari Laleh,
- Qinghe Zeng,
- Pascale Maille,
- Loetitia Favre,
- Anaïs Pujals,
- Christophe Klein,
- Céline Bazille,
- Lara R. Heij,
- Arnaud Uguen,
- Tom Luedde,
- Luca Di Tommaso,
- Aurélie Beaufrère,
- Augustin Chatain,
- Delphine Gastineau,
- Cong Trung Nguyen,
- Hiep Nguyen-Canh,
- Khuyen Nguyen Thi,
- Viviane Gnemmi,
- Rondell P. Graham,
- Frédéric Charlotte,
- Dominique Wendum,
- Mukul Vij,
- Daniela S. Allende,
- Federico Aucejo,
- Alba Diaz,
- Benjamin Rivière,
- Astrid Herrero,
- Katja Evert,
- Diego Francesco Calvisi,
- Jérémy Augustin,
- Wei Qiang Leow,
- Howard Ho Wai Leung,
- Emmanuel Boleslawski,
- Mohamed Rela,
- Arnaud François,
- Anthony Wing-Hung Cha,
- Alejandro Forner,
- Maria Reig,
- Manon Allaire,
- Olivier Scatton,
- Denis Chatelain,
- Camille Boulagnon-Rombi,
- Nathalie Sturm,
- Benjamin Menahem,
- Eric Frouin,
- David Tougeron,
- Christophe Tournigand,
- Emmanuelle Kempf,
- Haeryoung Kim,
- Massih Ningarhari,
- Sophie Michalak-Provost,
- Purva Gopal,
- Raffaele Brustia,
- Eric Vibert,
- Kornelius Schulze,
- Darius F. Rüther,
- Sören A. Weidemann,
- Rami Rhaiem,
- Jean-Michel Pawlotsky,
- Xuchen Zhang,
- Alain Luciani,
- Sébastien Mulé,
- Alexis Laurent,
- Giuliana Amaddeo,
- Hélène Regnault,
- Eleonora De Martin,
- Christine Sempoux,
- Pooja Navale,
- Maria Westerhoff,
- Regina Cheuk-Lam Lo,
- Jan Bednarsch,
- Annette Gouw,
- Catherine Guettier,
- Marie Lequoy,
- Kenichi Harada,
- Pimsiri Sripongpun,
- Poowadon Wetwittayaklang,
- Nicolas Loménie,
- Jarukit Tantipisit,
- Apichat Kaewdech,
- Jeanne Shen,
- Valérie Paradis,
- Stefano Caruso,
- Jakob Nikolas Kather
Affiliations
- Julien Calderaro
- Université Paris Est Créteil, INSERM, IMRB
- Narmin Ghaffari Laleh
- Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden
- Qinghe Zeng
- Centre d’Histologie, d’Imagerie et de Cytométrie (CHIC), Centre de Recherche des Cordeliers
- Pascale Maille
- Université Paris Est Créteil, INSERM, IMRB
- Loetitia Favre
- Université Paris Est Créteil, INSERM, IMRB
- Anaïs Pujals
- Université Paris Est Créteil, INSERM, IMRB
- Christophe Klein
- Centre d’Histologie, d’Imagerie et de Cytométrie (CHIC), Centre de Recherche des Cordeliers
- Céline Bazille
- Caen University Hospital, Department of Pathology
- Lara R. Heij
- Department of Surgery and Transplantation, University Hospital RWTH Aachen
- Arnaud Uguen
- CHRU Brest, Department of Pathology
- Tom Luedde
- Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine University Düsseldorf
- Luca Di Tommaso
- Department of Pathology, Humanitas University, Humanitas Clinical and Research Center, IRCCS, Rozzano
- Aurélie Beaufrère
- Assistance Publique–Hôpitaux de Paris, Beaujon University Hospital, Department of Pathology
- Augustin Chatain
- Inserm, U955, Team 18
- Delphine Gastineau
- Inserm, U955, Team 18
- Cong Trung Nguyen
- Department of Pathology, E Hospital, Hanoi Medical University
- Hiep Nguyen-Canh
- Pathology Center, Bachmai Hospital
- Khuyen Nguyen Thi
- Pathology and Molecular biology Center, National Cancer Hospital
- Viviane Gnemmi
- University Lille, UMR9020-U1277, Cancer Heterogeneity Plasticity and Resistance to Therapies
- Rondell P. Graham
- Department of Laboratory Medicine and Pathology, Mayo Clinic Rochester
- Frédéric Charlotte
- Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Pathology
- Dominique Wendum
- Assistance Publique-Hôpitaux de Paris, Saint-Antoine University Hospital, Department of Pathology
- Mukul Vij
- Department of Pathology, Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research
- Daniela S. Allende
- Department of Hepatobiliary Pathology, Cleveland Clinic Foundation
- Federico Aucejo
- Department of Gastrointestinal and Hepatobiliary Surgery, Cleveland Clinic Foundation
- Alba Diaz
- Barcelona Clinic Liver Cancer (BCLC) Group, Department of Pathology, Hospital Clínic de Barcelona, Universitat de Barcelona
- Benjamin Rivière
- Department of Pathology, Gui-de-Chauliac University Hospital, 80
- Astrid Herrero
- Department of Digestive and Hepatobiliary Surgery, Gui-de-Chauliac University Hospital, 80
- Katja Evert
- Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11
- Diego Francesco Calvisi
- Institute of Pathology, University of Regensburg, Franz-Josef-Strauß-Allee 11
- Jérémy Augustin
- Université Paris Est Créteil, INSERM, IMRB
- Wei Qiang Leow
- Department of Anatomical Pathology, Singapore General Hospital
- Howard Ho Wai Leung
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong
- Emmanuel Boleslawski
- CHU Lille, Department of Digestive and Hepatobiliary Surgery
- Mohamed Rela
- Dr Rela Institute and Medical Centre, Bharath Institute of Higher Education and Research
- Arnaud François
- Rouen University Hospital, Department of Pathology
- Anthony Wing-Hung Cha
- Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong
- Alejandro Forner
- Barcelona Clinic Liver Cancer (BCLC), Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, CIBEREHD, Universidad de Barcelona
- Maria Reig
- Barcelona Clinic Liver Cancer (BCLC), Liver Unit, Hospital Clinic of Barcelona, IDIBAPS, CIBEREHD, Universidad de Barcelona
- Manon Allaire
- Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Hepatology
- Olivier Scatton
- Assistance Publique-Hôpitaux de Paris, Pitié-Salpêtrière University Hospital, Department of Digestive and Hepatobiliary Surgery
- Denis Chatelain
- Centre Hospitalier Universitaire d’Amiens, Département de Pathologie
- Camille Boulagnon-Rombi
- Reims University Hospital, Department of Pathology
- Nathalie Sturm
- Department of Pathology, University Hospital
- Benjamin Menahem
- Caen University Hospital, Department of Digestive and Hepatobiliary Surgery
- Eric Frouin
- Poitiers University Hospital, Department of Pathology
- David Tougeron
- Poitiers University Hospital, Department of Hepatogastroenterology and Oncology
- Christophe Tournigand
- Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Medical Oncology
- Emmanuelle Kempf
- Assistance Publique-Hôpitaux de Paris, Henri Mondor-Albert Chenevier University Hospital, Department of Medical Oncology
- Haeryoung Kim
- Department of Pathology, Seoul National University Hospital, Seoul National University College of Medicine
- Massih Ningarhari
- CHU Lille, Department of Hepatology
- Sophie Michalak-Provost
- Angers University Hospital, Department of Pathology
- Purva Gopal
- Department of Pathology, UT Southwestern Medical Center
- Raffaele Brustia
- Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Digestive and Hepatobiliary Surgery
- Eric Vibert
- Assistance Publique-Hôpitaux de Paris, Paul Brousse University Hospital, Department of Digestive and Hepatobiliary Surgery
- Kornelius Schulze
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf
- Darius F. Rüther
- Department of Internal Medicine, University Medical Center Hamburg-Eppendorf
- Sören A. Weidemann
- Department of Pathology, University Medical Center Hamburg-Eppendorf
- Rami Rhaiem
- Reims University Hospital, Department of Digestive and Hepatobiliary Surgery
- Jean-Michel Pawlotsky
- Université Paris Est Créteil, INSERM, IMRB
- Xuchen Zhang
- Department of Pathology, Yale University School of Medicine
- Alain Luciani
- Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Medical Imaging
- Sébastien Mulé
- Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Medical Imaging
- Alexis Laurent
- Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Digestive and Hepatobiliary Surgery
- Giuliana Amaddeo
- Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Hepatology
- Hélène Regnault
- Assistance Publique-Hôpitaux de Paris, Henri Mondor University Hospital, Department of Hepatology
- Eleonora De Martin
- Assistance Publique-Hôpitaux de Paris, Paul Brousse University Hospital, Department of Hepatology
- Christine Sempoux
- Institute of Pathology, Lausanne University Hospital (CHUV), University of Lausanne (UNIL)
- Pooja Navale
- Department of Pathology and Immunology, Washington University in St. Louis
- Maria Westerhoff
- Department of Pathology University of Michigan
- Regina Cheuk-Lam Lo
- Department of Pathology, The University of Hong Kong, Pok Fu Lam
- Jan Bednarsch
- Department of Surgery and Transplantation, University Hospital RWTH Aachen
- Annette Gouw
- Department of Pathology and Medical Biology, University Medical Center Groningen
- Catherine Guettier
- Department of Surgery and Transplantation, University Hospital RWTH Aachen
- Marie Lequoy
- Assistance Publique-Hôpitaux de Paris, Saint Antoine University Hospital, Department of Hepatology
- Kenichi Harada
- Department of Human Pathology, Kanazawa University Graduate School of Medicine
- Pimsiri Sripongpun
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University
- Poowadon Wetwittayaklang
- Prince of Songkla University, Department of Pathology
- Nicolas Loménie
- Laboratoire d’Informatique Paris Descartes (LIPADE), Université Paris Cité
- Jarukit Tantipisit
- Prince of Songkla University, Department of Pathology
- Apichat Kaewdech
- Gastroenterology and Hepatology Unit, Division of Internal Medicine, Faculty of Medicine, Prince of Songkla University
- Jeanne Shen
- Center for Artificial Intelligence in Medicine and Imaging, Stanford University
- Valérie Paradis
- Assistance Publique–Hôpitaux de Paris, Beaujon University Hospital, Department of Pathology
- Stefano Caruso
- Université Paris Est Créteil, INSERM, IMRB
- Jakob Nikolas Kather
- Else Kroener Fresenius Center for Digital Health, Medical Faculty Carl Gustav Carus, Technical University Dresden
- DOI
- https://doi.org/10.1038/s41467-023-43749-3
- Journal volume & issue
-
Vol. 14,
no. 1
pp. 1 – 10
Abstract
Abstract Primary liver cancer arises either from hepatocytic or biliary lineage cells, giving rise to hepatocellular carcinoma (HCC) or intrahepatic cholangiocarcinoma (ICCA). Combined hepatocellular- cholangiocarcinomas (cHCC-CCA) exhibit equivocal or mixed features of both, causing diagnostic uncertainty and difficulty in determining proper management. Here, we perform a comprehensive deep learning-based phenotyping of multiple cohorts of patients. We show that deep learning can reproduce the diagnosis of HCC vs. CCA with a high performance. We analyze a series of 405 cHCC-CCA patients and demonstrate that the model can reclassify the tumors as HCC or ICCA, and that the predictions are consistent with clinical outcomes, genetic alterations and in situ spatial gene expression profiling. This type of approach could improve treatment decisions and ultimately clinical outcome for patients with rare and biphenotypic cancers such as cHCC-CCA.
