IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v14y2023i1d10.1038_s41467-023-39996-z.html
   My bibliography  Save this article

Obesity-associated changes in molecular biology of primary breast cancer

Author

Listed:
  • Ha-Linh Nguyen

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Tatjana Geukens

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Marion Maetens

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Samuel Aparicio

    (BC Cancer Research Centre
    University of British Columbia)

  • Ayse Bassez

    (Department of Human Genetics
    VIB Center for Cancer Biology)

  • Ake Borg

    (Lund University
    Lund University Cancer Center Lund
    Lund University
    Lund University)

  • Jane Brock

    (Brigham and Women’s Hospital)

  • Annegien Broeks

    (Antoni van Leeuwenhoek, the Netherlands Cancer Institute)

  • Carlos Caldas

    (Cancer Research UK Cambridge Institute and Department of Oncology, Li Ka Shing Centre, University of Cambridge)

  • Fatima Cardoso

    (Breast Unit, Champalimaud Clinical Center/Champalimaud Foundation)

  • Maxim Schepper

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Mauro Delorenzi

    (University of Lausanne
    SIB Swiss Institute of Bioinformatics, Bioinformatics Core Facility)

  • Caroline A. Drukker

    (Department of Surgical Oncology, Antoni van Leeuwenhoek Hospital)

  • Annuska M. Glas

    (Agendia)

  • Andrew R. Green

    (University of Nottingham)

  • Edoardo Isnaldi

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Jórunn Eyfjörð

    (University of Iceland)

  • Hazem Khout

    (University Hospitals of Leicester NHS Trust)

  • Stian Knappskog

    (University of Bergen
    Haukeland University Hospital)

  • Savitri Krishnamurthy

    (The University of Texas MD Anderson Cancer Center)

  • Sunil R. Lakhani

    (The University of Queensland
    The Royal Brisbane and Women’s Hospital)

  • Anita Langerod

    (Oslo University Hospital)

  • John W. M. Martens

    (Erasmus University Medical Center)

  • Amy E. McCart Reed

    (The University of Queensland)

  • Leigh Murphy

    (University of Manitoba and Cancer Care Manitoba Research Institute)

  • Stefan Naulaerts

    (Laboratory of Cell Stress & Immunity, Department of Cellular & Molecular Medicine)

  • Serena Nik-Zainal

    (University of Cambridge
    University of Cambridge)

  • Ines Nevelsteen

    (University Hospitals Leuven)

  • Patrick Neven

    (University Hospitals Leuven)

  • Martine Piccart

    (Institut Jules Bordet and Université Libre de Bruxelles)

  • Coralie Poncet

    (European Organisation for Research and Treatment of Cancer (EORTC) Headquarters)

  • Kevin Punie

    (Leuven Cancer Institute and University Hospitals Leuven)

  • Colin Purdie

    (University of Dundee, NHS Tayside)

  • Emad A. Rakha

    (University of Nottingham
    Nottingham University Hospital NHS Trust, City Hospital Campus)

  • Andrea Richardson

    (Johns Hopkins University School of Medicine)

  • Emiel Rutgers

    (Netherlands Cancer Institute)

  • Anne Vincent-Salomon

    (PSL Research University)

  • Peter T. Simpson

    (The University of Queensland)

  • Marjanka K. Schmidt

    (Netherlands Cancer Institute—Antoni van Leeuwenhoek Hospital)

  • Christos Sotiriou

    (Institut Jules Bordet, Universite Libre de Bruxelles)

  • Paul N. Span

    (Radboud University Medical Center)

  • Kiat Tee Benita Tan

    (Sengkang General Hospital
    Singapore General Hospital
    National Cancer Centre)

  • Alastair Thompson

    (Dan L Duncan Comprehensive Cancer Center, Baylor College of Medicine)

  • Stefania Tommasi

    (Molecular Diagnostics and Pharmacogenetics Unit, IRCCS Istituto Tumouri “Giovanni Paolo II”)

  • Karen Baelen

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Marc Vijver

    (Amsterdam University Medical Centers, Cancer Center Amsterdam, University of Amsterdam)

  • Steven Laere

    (Center for Oncological Research (CORE), Integrated Personalized and Precision Oncology Network (IPPON), University of Antwerp)

  • Laura van’t Veer

    (UCSF Helen Diller Family Comprehensive Cancer Center)

  • Giuseppe Viale

    (IEO, European Institute of Oncology IRCCS
    University of Milan)

  • Alain Viari

    (Synergie Lyon Cancer, Plateforme de Bio-informatique ‘Gilles Thomas’)

  • Hanne Vos

    (University Hospitals Leuven)

  • Anke T. Witteveen

    (Agendia)

  • Hans Wildiers

    (Leuven Cancer Institute and University Hospitals Leuven)

  • Giuseppe Floris

    (University Hospitals Leuven)

  • Abhishek D. Garg

    (Laboratory of Cell Stress & Immunity, Department of Cellular & Molecular Medicine)

  • Ann Smeets

    (University Hospitals Leuven)

  • Diether Lambrechts

    (Department of Human Genetics
    VIB Center for Cancer Biology)

  • Elia Biganzoli

    (Università degli Studi di Milano)

  • François Richard

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

  • Christine Desmedt

    (Laboratory for Translational Breast Cancer Research, Department of Oncology)

Abstract

Obesity is associated with an increased risk of developing breast cancer (BC) and worse prognosis in BC patients, yet its impact on BC biology remains understudied in humans. This study investigates how the biology of untreated primary BC differs according to patients’ body mass index (BMI) using data from >2,000 patients. We identify several genomic alterations that are differentially prevalent in overweight or obese patients compared to lean patients. We report evidence supporting an ageing accelerating effect of obesity at the genetic level. We show that BMI-associated differences in bulk transcriptomic profile are subtle, while single cell profiling allows detection of more pronounced changes in different cell compartments. These analyses further reveal an elevated and unresolved inflammation of the BC tumor microenvironment associated with obesity, with distinct characteristics contingent on the estrogen receptor status. Collectively, our analyses imply that obesity is associated with an inflammaging-like phenotype. We conclude that patient adiposity may play a significant role in the heterogeneity of BC and should be considered for BC treatment tailoring.

Suggested Citation

  • Ha-Linh Nguyen & Tatjana Geukens & Marion Maetens & Samuel Aparicio & Ayse Bassez & Ake Borg & Jane Brock & Annegien Broeks & Carlos Caldas & Fatima Cardoso & Maxim Schepper & Mauro Delorenzi & Caroli, 2023. "Obesity-associated changes in molecular biology of primary breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
  • Handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39996-z
    DOI: 10.1038/s41467-023-39996-z
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-023-39996-z
    File Function: Abstract
    Download Restriction: no

    File URL: https://libkey.io/10.1038/s41467-023-39996-z?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Christina Curtis & Sohrab P. Shah & Suet-Feung Chin & Gulisa Turashvili & Oscar M. Rueda & Mark J. Dunning & Doug Speed & Andy G. Lynch & Shamith Samarajiwa & Yinyin Yuan & Stefan Gräf & Gavin Ha & Gh, 2012. "The genomic and transcriptomic architecture of 2,000 breast tumours reveals novel subgroups," Nature, Nature, vol. 486(7403), pages 346-352, June.
    2. Serena Nik-Zainal & Helen Davies & Johan Staaf & Manasa Ramakrishna & Dominik Glodzik & Xueqing Zou & Inigo Martincorena & Ludmil B. Alexandrov & Sancha Martin & David C. Wedge & Peter Van Loo & Young, 2016. "Landscape of somatic mutations in 560 breast cancer whole-genome sequences," Nature, Nature, vol. 534(7605), pages 47-54, June.
    3. Suoqin Jin & Christian F. Guerrero-Juarez & Lihua Zhang & Ivan Chang & Raul Ramos & Chen-Hsiang Kuan & Peggy Myung & Maksim V. Plikus & Qing Nie, 2021. "Inference and analysis of cell-cell communication using CellChat," Nature Communications, Nature, vol. 12(1), pages 1-20, December.
    4. Yang Claire Yang & Christine E. Walsh & Moira P. Johnson & Daniel W. Belsky & Max Reason & Patrick Curran & Allison E. Aiello & Marianne Chanti-Ketterl & Kathleen Mullan Harris, 2021. "Life-course trajectories of body mass index from adolescence to old age: Racial and educational disparities," Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, vol. 118(17), pages 2020167118-, April.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Zhe Jiang & YoungJun Ju & Amjad Ali & Philip E. D. Chung & Patryk Skowron & Dong-Yu Wang & Mariusz Shrestha & Huiqin Li & Jeff C. Liu & Ioulia Vorobieva & Ronak Ghanbari-Azarnier & Ethel Mwewa & Maria, 2023. "Distinct shared and compartment-enriched oncogenic networks drive primary versus metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-22, December.
    2. S. Mouron & M. J. Bueno & A. Lluch & L. Manso & I. Calvo & J. Cortes & J. A. Garcia-Saenz & M. Gil-Gil & N. Martinez-Janez & J. V. Apala & E. Caleiras & Pilar Ximénez-Embún & J. Muñoz & L. Gonzalez-Co, 2022. "Phosphoproteomic analysis of neoadjuvant breast cancer suggests that increased sensitivity to paclitaxel is driven by CDK4 and filamin A," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    3. Amanda Fitzpatrick & Marjan Iravani & Adam Mills & David Vicente & Thanussuyah Alaguthurai & Ioannis Roxanis & Nicholas C. Turner & Syed Haider & Andrew N. J. Tutt & Clare M. Isacke, 2023. "Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    4. Aleix Prat & Fara Brasó-Maristany & Olga Martínez-Sáez & Esther Sanfeliu & Youli Xia & Meritxell Bellet & Patricia Galván & Débora Martínez & Tomás Pascual & Mercedes Marín-Aguilera & Anna Rodríguez &, 2023. "Circulating tumor DNA reveals complex biological features with clinical relevance in metastatic breast cancer," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    5. Michelle Dietzen & Haoran Zhai & Olivia Lucas & Oriol Pich & Christopher Barrington & Wei-Ting Lu & Sophia Ward & Yanping Guo & Robert E. Hynds & Simone Zaccaria & Charles Swanton & Nicholas McGranaha, 2024. "Replication timing alterations are associated with mutation acquisition during breast and lung cancer evolution," Nature Communications, Nature, vol. 15(1), pages 1-23, December.
    6. Yanchuan Li & Huamei Li & Cheng Peng & Ge Meng & Yijun Lu & Honglin Liu & Li Cui & Huan Zhou & Zhu Xu & Lingyun Sun & Lihong Liu & Qing Xiong & Beicheng Sun & Shiping Jiao, 2024. "Unraveling the spatial organization and development of human thymocytes through integration of spatial transcriptomics and single-cell multi-omics profiling," Nature Communications, Nature, vol. 15(1), pages 1-25, December.
    7. Liang, Weijuan & Zhang, Qingzhao & Ma, Shuangge, 2024. "Hierarchical false discovery rate control for high-dimensional survival analysis with interactions," Computational Statistics & Data Analysis, Elsevier, vol. 192(C).
    8. Glei, Dana A. & Weinstein, Maxine, 2023. "Economic distress, obesity, and the rise in pain," Social Science & Medicine, Elsevier, vol. 339(C).
    9. Lichun Ma & Sophia Heinrich & Limin Wang & Friederike L. Keggenhoff & Subreen Khatib & Marshonna Forgues & Michael Kelly & Stephen M. Hewitt & Areeba Saif & Jonathan M. Hernandez & Donna Mabry & Roman, 2022. "Multiregional single-cell dissection of tumor and immune cells reveals stable lock-and-key features in liver cancer," Nature Communications, Nature, vol. 13(1), pages 1-17, December.
    10. Qingnan Liang & Yuefan Huang & Shan He & Ken Chen, 2023. "Pathway centric analysis for single-cell RNA-seq and spatial transcriptomics data with GSDensity," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    11. Faith H. Brennan & Yang Li & Cankun Wang & Anjun Ma & Qi Guo & Yi Li & Nicole Pukos & Warren A. Campbell & Kristina G. Witcher & Zhen Guan & Kristina A. Kigerl & Jodie C. E. Hall & Jonathan P. Godbout, 2022. "Microglia coordinate cellular interactions during spinal cord repair in mice," Nature Communications, Nature, vol. 13(1), pages 1-20, December.
    12. Sandra Curras-Alonso & Juliette Soulier & Thomas Defard & Christian Weber & Sophie Heinrich & Hugo Laporte & Sophie Leboucher & Sonia Lameiras & Marie Dutreix & Vincent Favaudon & Florian Massip & Tho, 2023. "An interactive murine single-cell atlas of the lung responses to radiation injury," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    13. Hugh Chen & Scott M. Lundberg & Su-In Lee, 2022. "Explaining a series of models by propagating Shapley values," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    14. Moujtaba Y. Kasmani & Paytsar Topchyan & Ashley K. Brown & Ryan J. Brown & Xiaopeng Wu & Yao Chen & Achia Khatun & Donia Alson & Yue Wu & Robert Burns & Chien-Wei Lin & Matthew R. Kudek & Jie Sun & We, 2023. "A spatial sequencing atlas of age-induced changes in the lung during influenza infection," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    15. Wei Yang & Li-Bo Liu & Feng-Liang Liu & Yan-Hua Wu & Zi-Da Zhen & Dong-Ying Fan & Zi-Yang Sheng & Zheng-Ran Song & Jia-Tong Chang & Yong-Tang Zheng & Jing An & Pei-Gang Wang, 2023. "Single-cell RNA sequencing reveals the fragility of male spermatogenic cells to Zika virus-induced complement activation," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    16. Luke Simpson & Andrew Strange & Doris Klisch & Sophie Kraunsoe & Takuya Azami & Daniel Goszczynski & Triet Minh & Benjamin Planells & Nadine Holmes & Fei Sang & Sonal Henson & Matthew Loose & Jennifer, 2024. "A single-cell atlas of pig gastrulation as a resource for comparative embryology," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    17. Camilla Tombari & Alessandro Zannini & Rebecca Bertolio & Silvia Pedretti & Matteo Audano & Luca Triboli & Valeria Cancila & Davide Vacca & Manuel Caputo & Sara Donzelli & Ilenia Segatto & Simone Vodr, 2023. "Mutant p53 sustains serine-glycine synthesis and essential amino acids intake promoting breast cancer growth," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    18. Xiaojian Lu & Yanwei Luo & Xichen Nie & Bailing Zhang & Xiaoyan Wang & Ran Li & Guangmin Liu & Qianyin Zhou & Zhizhong Liu & Liqing Fan & James M. Hotaling & Zhe Zhang & Hao Bo & Jingtao Guo, 2023. "Single-cell multi-omics analysis of human testicular germ cell tumor reveals its molecular features and microenvironment," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    19. Anjun Ma & Xiaoying Wang & Jingxian Li & Cankun Wang & Tong Xiao & Yuntao Liu & Hao Cheng & Juexin Wang & Yang Li & Yuzhou Chang & Jinpu Li & Duolin Wang & Yuexu Jiang & Li Su & Gang Xin & Shaopeng Gu, 2023. "Single-cell biological network inference using a heterogeneous graph transformer," Nature Communications, Nature, vol. 14(1), pages 1-18, December.
    20. Jeff DeMartino & Michael T. Meister & Lindy L. Visser & Mariël Brok & Marian J. A. Groot Koerkamp & Amber K. L. Wezenaar & Laura S. Hiemcke-Jiwa & Terezinha Souza & Johannes H. M. Merks & Anne C. Rios, 2023. "Single-cell transcriptomics reveals immune suppression and cell states predictive of patient outcomes in rhabdomyosarcoma," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-39996-z. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.