Metabolic pathway-based subtypes associate glycan biosynthesis and treatment response in head and neck cancer.

Journal

NPJ precision oncology
ISSN: 2397-768X
Titre abrégé: NPJ Precis Oncol
Pays: England
ID NLM: 101708166

Informations de publication

Date de publication:
23 May 2024
Historique:
received: 10 08 2023
accepted: 08 05 2024
medline: 24 5 2024
pubmed: 24 5 2024
entrez: 23 5 2024
Statut: epublish

Résumé

Head and Neck Squamous Cell Carcinoma (HNSCC) is a heterogeneous malignancy that remains a significant challenge in clinical management due to frequent treatment failures and pronounced therapy resistance. While metabolic dysregulation appears to be a critical factor in this scenario, comprehensive analyses of the metabolic HNSCC landscape and its impact on clinical outcomes are lacking. This study utilized transcriptomic data from four independent clinical cohorts to investigate metabolic heterogeneity in HNSCC and define metabolic pathway-based subtypes (MPS). In HPV-negative HNSCCs, MPS1 and MPS2 were identified, while MPS3 was enriched in HPV-positive cases. MPS classification was associated with clinical outcome post adjuvant radio(chemo)therapy, with MPS1 consistently exhibiting the highest risk of therapeutic failure. MPS1 was uniquely characterized by upregulation of glycan (particularly chondroitin/dermatan sulfate) metabolism genes. Immunohistochemistry and pilot mass spectrometry imaging analyses confirmed this at metabolite level. The histological context and single-cell RNA sequencing data identified the malignant cells as key contributors. Globally, MPS1 was distinguished by a unique transcriptomic landscape associated with increased disease aggressiveness, featuring motifs related to epithelial-mesenchymal transition, immune signaling, cancer stemness, tumor microenvironment assembly, and oncogenic signaling. This translated into a distinct histological appearance marked by extensive extracellular matrix remodeling, abundant spindle-shaped cancer-associated fibroblasts, and intimately intertwined populations of malignant and stromal cells. Proof-of-concept data from orthotopic xenotransplants replicated the MPS phenotypes on the histological and transcriptome levels. In summary, this study introduces a metabolic pathway-based classification of HNSCC, pinpointing glycan metabolism-enriched MPS1 as the most challenging subgroup that necessitates alternative therapeutic strategies.

Identifiants

DOI: 10.1038/s41698-024-00602-0 PMID: 38783045
pubmed: 38783045
doi: 10.1038/s41698-024-00602-0
pii: 10.1038/s41698-024-00602-0
doi:

Types de publication

Journal Article

Langues

eng

Pagination

116

Subventions

Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 02NUK061A
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 02NUK061A
Organisme : Bundesministerium für Bildung und Forschung (Federal Ministry of Education and Research)
ID : 02NUK061C

Informations de copyright

© 2024. The Author(s).

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Auteurs

Benedek Dankó (B)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.

Julia Hess (J)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Kristian Unger (K)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Bavarian Cancer Research Center (BZKF), Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Daniel Samaga (D)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.

Christoph Walz (C)

Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.

Axel Walch (A)

Research Unit Analytical Pathology, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.

Na Sun (N)

Research Unit Analytical Pathology, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.

Philipp Baumeister (P)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Bavarian Cancer Research Center (BZKF), Munich, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Comprehensive Cancer Center, Munich, Germany.

Peter Y F Zeng (PYF)

Department of Pathology and Laboratory Medicine, University of Western Ontario, London, ON, Canada.
Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, ON, Canada.
ORCID: 0000-0002-6818-8236

Franziska Walter (F)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Sebastian Marschner (S)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Comprehensive Cancer Center, Munich, Germany.
ORCID: 0000-0002-8121-358X

Richard Späth (R)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Comprehensive Cancer Center, Munich, Germany.

Olivier Gires (O)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
ORCID: 0000-0002-2292-7064

Timm Herkommer (T)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.

Ramin Dazeh (R)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.

Thaina Matos (T)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.

Lisa Kreutzer (L)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.

Johann Matschke (J)

Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.
German Cancer Consortium (DKTK) partner site Essen a partnership between DKFZ and University Hospital, Essen, Germany.
ORCID: 0000-0003-4878-8741

Katharina Eul (K)

Institute of Cell Biology (Cancer Research), University Hospital Essen, University of Duisburg-Essen, Essen, Germany.

Frederick Klauschen (F)

Bavarian Cancer Research Center (BZKF), Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Institute of Pathology, Faculty of Medicine, LMU Munich, Munich, Germany.
Comprehensive Cancer Center, Munich, Germany.

Ulrike Pflugradt (U)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Comprehensive Cancer Center, Munich, Germany.

Martin Canis (M)

Department of Otorhinolaryngology, Head and Neck Surgery, LMU University Hospital, LMU Munich, Munich, Germany.
Comprehensive Cancer Center, Munich, Germany.

Ute Ganswindt (U)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Department of Radiation Oncology, Innsbruck Medical University, Innsbruck, Austria.
Comprehensive Cancer Center Innsbruck, Innsbruck, Austria.

Joe S Mymryk (JS)

Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, ON, Canada.
Department of Microbiology & Immunology, University of Western Ontario, London, ON, Canada.
Department of Oncology, University of Western Ontario, London, ON, Canada.

Barbara Wollenberg (B)

Comprehensive Cancer Center, Munich, Germany.
Clinic of Otorhinolaryngology, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
Department of Otorhinolaryngology, University of Luebeck, Luebeck, Germany.

Anthony C Nichols (AC)

Department of Pathology and Laboratory Medicine, University of Western Ontario, London, ON, Canada.
Department of Otolaryngology - Head and Neck Surgery, University of Western Ontario, London, ON, Canada.
Department of Oncology, University of Western Ontario, London, ON, Canada.
ORCID: 0000-0002-0760-980X

Claus Belka (C)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Bavarian Cancer Research Center (BZKF), Munich, Germany.
German Cancer Consortium (DKTK), Partner Site Munich, German Cancer Research Center (DKFZ), Heidelberg, Germany.
Comprehensive Cancer Center, Munich, Germany.

Horst Zitzelsberger (H)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.

Kirsten Lauber (K)

Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany.
Department of Radiation Oncology, University Hospital, LMU Munich, Munich, Germany.
Comprehensive Cancer Center, Munich, Germany.
ORCID: 0000-0002-8141-0452

Martin Selmansberger (M)

Research Unit Translational Metabolic Oncology, Institute for Diabetes and Cancer, Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany. martin.selmansberger@helmholtz-munich.de.
Clinical Cooperation Group "Personalized Radiotherapy in Head and Neck Cancer, " Helmholtz Zentrum München Deutsches Forschungszentrum für Gesundheit und Umwelt (GmbH), Neuherberg, Germany. martin.selmansberger@helmholtz-munich.de.
ORCID: 0000-0002-6700-946X

Classifications MeSH