Integrated analysis of cervical squamous cell carcinoma cohorts from three continents reveals conserved subtypes of prognostic significance.


Journal

Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555

Informations de publication

Date de publication:
07 10 2022
Historique:
received: 03 12 2021
accepted: 15 09 2022
entrez: 7 10 2022
pubmed: 8 10 2022
medline: 12 10 2022
Statut: epublish

Résumé

Human papillomavirus (HPV)-associated cervical cancer is a leading cause of cancer deaths in women. Here we present an integrated multi-omic analysis of 643 cervical squamous cell carcinomas (CSCC, the most common histological variant of cervical cancer), representing patient populations from the USA, Europe and Sub-Saharan Africa and identify two CSCC subtypes (C1 and C2) with differing prognosis. C1 and C2 tumours can be driven by either of the two most common HPV types in cervical cancer (16 and 18) and while HPV16 and HPV18 are overrepresented among C1 and C2 tumours respectively, the prognostic difference between groups is not due to HPV type. C2 tumours, which comprise approximately 20% of CSCCs across these cohorts, display distinct genomic alterations, including loss or mutation of the STK11 tumour suppressor gene, increased expression of several immune checkpoint genes and differences in the tumour immune microenvironment that may explain the shorter survival associated with this group. In conclusion, we identify two therapy-relevant CSCC subtypes that share the same defining characteristics across three geographically diverse cohorts.

Identifiants

pubmed: 36207323
doi: 10.1038/s41467-022-33544-x
pii: 10.1038/s41467-022-33544-x
pmc: PMC9547055
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

5818

Subventions

Organisme : Medical Research Council
ID : MR/M025411/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/R009295/1
Pays : United Kingdom
Organisme : Biotechnology and Biological Sciences Research Council
ID : BB/V010271/1
Pays : United Kingdom
Organisme : Cancer Research UK
ID : A25825
Pays : United Kingdom

Informations de copyright

© 2022. The Author(s).

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Auteurs

Ankur Chakravarthy (A)

Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada.

Ian Reddin (I)

Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

Stephen Henderson (S)

UCL Cancer Institute, Bill Lyons Informatics Centre, University College London, London, UK.

Cindy Dong (C)

School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

Nerissa Kirkwood (N)

School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

Maxmilan Jeyakumar (M)

School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

Daniela Rothschild Rodriguez (DR)

School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

Natalia Gonzalez Martinez (NG)

School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

Jacqueline McDermott (J)

UCL Cancer Institute, University College London, London, UK.

Xiaoping Su (X)

MD Anderson Cancer Center, Houston, TX, USA.

Nagayasau Egawa (N)

Department of Pathology, University of Cambridge, Cambridge, UK.

Christina S Fjeldbo (CS)

Department of Radiation Biology, Oslo University Hospital, Oslo, Norway.

Vilde Eide Skingen (VE)

Department of Radiation Biology, Oslo University Hospital, Oslo, Norway.

Heidi Lyng (H)

Department of Radiation Biology, Oslo University Hospital, Oslo, Norway.
Department of Physics, University of Oslo, Oslo, Norway.

Mari Kyllesø Halle (MK)

Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.

Camilla Krakstad (C)

Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.

Afschin Soleiman (A)

INNPATH, Institute of Pathology, Tirol Kliniken Innsbruck, Innsbruck, Austria.

Susanne Sprung (S)

Institute of Pathology, Medical University of Innsbruck, Innsbruck, Austria.

Matt Lechner (M)

UCL Cancer Institute, University College London, London, UK.

Peter J I Ellis (PJI)

School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

Mark Wass (M)

School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

Martin Michaelis (M)

School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK.

Heidi Fiegl (H)

Department of Obstetrics and Gynaecology, Medical University of Innsbruck, Innsbruck, Austria.

Helga Salvesen (H)

Department of Obstetrics and Gynaecology, Haukeland University Hospital, Bergen, Norway; Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, Bergen, Norway.

Gareth J Thomas (GJ)

Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK.

John Doorbar (J)

Department of Pathology, University of Cambridge, Cambridge, UK.

Kerry Chester (K)

UCL Cancer Institute, University College London, London, UK. k.chester@ucl.ac.uk.

Andrew Feber (A)

Centre for Molecular Pathology, Royal Marsden Hospital Trust, London, UK. a.feber@ucl.ac.uk.
Division of Surgery and Interventional Science, University College London, London, UK. a.feber@ucl.ac.uk.

Tim R Fenton (TR)

Cancer Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. t.r.fenton@soton.ac.uk.
School of Biosciences, Division of Natural Sciences, University of Kent, Canterbury, UK. t.r.fenton@soton.ac.uk.
Institute for Life Sciences, University of Southampton, Southampton, UK. t.r.fenton@soton.ac.uk.

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