IDEAS home Printed from https://ideas.repec.org/a/nat/natcom/v15y2024i1d10.1038_s41467-024-47271-y.html
   My bibliography  Save this article

Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones

Author

Listed:
  • Elena Denisenko

    (The University of Western Australia, Nedlands)

  • Leanne Kock

    (The University of Western Australia, Nedlands
    Children’s Hospital of Eastern Ontario Research Institute)

  • Adeline Tan

    (Clinipath, Sonic Healthcare)

  • Aaron B. Beasley

    (Edith Cowan University)

  • Maria Beilin

    (Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital)

  • Matthew E. Jones

    (The University of Western Australia, Nedlands)

  • Rui Hou

    (The University of Western Australia, Nedlands)

  • Dáithí Ó Muirí

    (The University of Western Australia, Nedlands)

  • Sanela Bilic

    (Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital)

  • G. Raj K. A. Mohan

    (Bendat Family Comprehensive Cancer Centre, St John of God Subiaco Hospital
    University of Notre Dame)

  • Stuart Salfinger

    (Western Australian Gynae and Surgery)

  • Simon Fox

    (The University of Western Australia, Nedlands)

  • Khaing P. W. Hmon

    (The University of Western Australia, Nedlands)

  • Yen Yeow

    (The University of Western Australia, Nedlands)

  • Youngmi Kim

    (NanoString Technologies)

  • Rhea John

    (NanoString Technologies)

  • Tami S. Gilderman

    (NanoString Technologies)

  • Emily Killingbeck

    (NanoString Technologies)

  • Elin S. Gray

    (Edith Cowan University)

  • Paul A. Cohen

    (University of Western Australia
    The University of Notre Dame Australia)

  • Yu Yu

    (University of Western Australia
    Curtin University
    Curtin University B305)

  • Alistair R. R. Forrest

    (The University of Western Australia, Nedlands)

Abstract

High-grade serous ovarian carcinoma (HGSOC) is genetically unstable and characterised by the presence of subclones with distinct genotypes. Intratumoural heterogeneity is linked to recurrence, chemotherapy resistance, and poor prognosis. Here, we use spatial transcriptomics to identify HGSOC subclones and study their association with infiltrating cell populations. Visium spatial transcriptomics reveals multiple tumour subclones with different copy number alterations present within individual tumour sections. These subclones differentially express various ligands and receptors and are predicted to differentially associate with different stromal and immune cell populations. In one sample, CosMx single molecule imaging reveals subclones differentially associating with immune cell populations, fibroblasts, and endothelial cells. Cell-to-cell communication analysis identifies subclone-specific signalling to stromal and immune cells and multiple subclone-specific autocrine loops. Our study highlights the high degree of subclonal heterogeneity in HGSOC and suggests that subclone-specific ligand and receptor expression patterns likely modulate how HGSOC cells interact with their local microenvironment.

Suggested Citation

  • Elena Denisenko & Leanne Kock & Adeline Tan & Aaron B. Beasley & Maria Beilin & Matthew E. Jones & Rui Hou & Dáithí Ó Muirí & Sanela Bilic & G. Raj K. A. Mohan & Stuart Salfinger & Simon Fox & Khaing , 2024. "Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones," Nature Communications, Nature, vol. 15(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47271-y
    DOI: 10.1038/s41467-024-47271-y
    as

    Download full text from publisher

    File URL: https://www.nature.com/articles/s41467-024-47271-y
    File Function: Abstract
    Download Restriction: no
    File URL: https://libkey.io/10.1038/s41467-024-47271-y?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. S. Intidhar Labidi-Galy & Eniko Papp & Dorothy Hallberg & Noushin Niknafs & Vilmos Adleff & Michael Noe & Rohit Bhattacharya & Marian Novak & Siân Jones & Jillian Phallen & Carolyn A. Hruban & Michell, 2017. "High grade serous ovarian carcinomas originate in the fallopian tube," Nature Communications, Nature, vol. 8(1), pages 1-11, December.
    2. Viktor A. Adalsteinsson & Gavin Ha & Samuel S. Freeman & Atish D. Choudhury & Daniel G. Stover & Heather A. Parsons & Gregory Gydush & Sarah C. Reed & Denisse Rotem & Justin Rhoades & Denis Loginov & , 2017. "Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors," Nature Communications, Nature, vol. 8(1), pages 1-13, December.
    3. Rui Hou & Elena Denisenko & Huan Ting Ong & Jordan A. Ramilowski & Alistair R. R. Forrest, 2020. "Predicting cell-to-cell communication networks using NATMI," Nature Communications, Nature, vol. 11(1), pages 1-11, December.
    4. Andrew Erickson & Mengxiao He & Emelie Berglund & Maja Marklund & Reza Mirzazadeh & Niklas Schultz & Linda Kvastad & Alma Andersson & Ludvig Bergenstråhle & Joseph Bergenstråhle & Ludvig Larsson & Lei, 2022. "Spatially resolved clonal copy number alterations in benign and malignant tissue," Nature, Nature, vol. 608(7922), pages 360-367, August.
    5. Shuang Zhang & Igor Dolgalev & Tao Zhang & Hao Ran & Douglas A. Levine & Benjamin G. Neel, 2019. "Both fallopian tube and ovarian surface epithelium are cells-of-origin for high-grade serous ovarian carcinoma," Nature Communications, Nature, vol. 10(1), pages 1-16, December.
    6. Ann-Marie Patch & Elizabeth L. Christie & Dariush Etemadmoghadam & Dale W. Garsed & Joshy George & Sian Fereday & Katia Nones & Prue Cowin & Kathryn Alsop & Peter J. Bailey & Karin S. Kassahn & Felici, 2015. "Whole–genome characterization of chemoresistant ovarian cancer," Nature, Nature, vol. 521(7553), pages 489-494, May.
    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. Jennifer B. Shah & Dana Pueschl & Bradley Wubbenhorst & Mengyao Fan & John Pluta & Kurt D’Andrea & Anna P. Hubert & Jake S. Shilan & Wenting Zhou & Adam A. Kraya & Alba Llop Guevara & Catherine Ruan &, 2022. "Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    2. Mireia Crispin-Ortuzar & Ramona Woitek & Marika A. V. Reinius & Elizabeth Moore & Lucian Beer & Vlad Bura & Leonardo Rundo & Cathal McCague & Stephan Ursprung & Lorena Escudero Sanchez & Paula Martin-, 2023. "Integrated radiogenomics models predict response to neoadjuvant chemotherapy in high grade serous ovarian cancer," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    3. Liana Goehring & Sarah Keegan & Sudipta Lahiri & Wenxin Xia & Michael Kong & Judit Jimenez-Sainz & Dipika Gupta & Ronny Drapkin & Ryan B. Jensen & Duncan J. Smith & Eli Rothenberg & David Fenyö & Tony, 2024. "Dormant origin firing promotes head-on transcription-replication conflicts at transcription termination sites in response to BRCA2 deficiency," Nature Communications, Nature, vol. 15(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. Maria Pouyiourou & Bianca N. Kraft & Timothy Wohlfromm & Michael Stahl & Boris Kubuschok & Harald Löffler & Ulrich T. Hacker & Gerdt Hübner & Lena Weiss & Michael Bitzer & Thomas Ernst & Philipp Schüt, 2023. "Nivolumab and ipilimumab in recurrent or refractory cancer of unknown primary: a phase II trial," Nature Communications, Nature, vol. 14(1), pages 1-21, December.
    6. Iris van ’t Erve & Bahar Alipanahi & Keith Lumbard & Zachary L. Skidmore & Lorenzo Rinaldi & Laurel K. Millberg & Jacob Carey & Bryan Chesnick & Stephen Cristiano & Carter Portwood & Tony Wu & Erica P, 2024. "Cancer treatment monitoring using cell-free DNA fragmentomes," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    7. Mingyun Bae & Gyuhee Kim & Tae-Rim Lee & Jin Mo Ahn & Hyunwook Park & Sook Ryun Park & Ki Byung Song & Eunsung Jun & Dongryul Oh & Jeong-Won Lee & Young Sik Park & Ki-Won Song & Jeong-Sik Byeon & Bo H, 2023. "Integrative modeling of tumor genomes and epigenomes for enhanced cancer diagnosis by cell-free DNA," Nature Communications, Nature, vol. 14(1), pages 1-15, December.
    8. Jonathan C. M. Wan & Dennis Stephens & Lingqi Luo & James R. White & Caitlin M. Stewart & Benoît Rousseau & Dana W. Y. Tsui & Luis A. Diaz, 2022. "Genome-wide mutational signatures in low-coverage whole genome sequencing of cell-free DNA," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    9. Magnus Zethoven & Luciano Martelotto & Andrew Pattison & Blake Bowen & Shiva Balachander & Aidan Flynn & Fernando J. Rossello & Annette Hogg & Julie A. Miller & Zdenek Frysak & Sean Grimmond & Lauren , 2022. "Single-nuclei and bulk-tissue gene-expression analysis of pheochromocytoma and paraganglioma links disease subtypes with tumor microenvironment," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    10. Kate E. Stanley & Tatjana Jatsenko & Stefania Tuveri & Dhanya Sudhakaran & Lore Lannoo & Kristel Calsteren & Marie Borre & Ilse Parijs & Leen Coillie & Kris Bogaert & Rodrigo Almeida Toledo & Liesbeth, 2024. "Cell type signatures in cell-free DNA fragmentation profiles reveal disease biology," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    11. Erick Armingol & Hratch M. Baghdassarian & Cameron Martino & Araceli Perez-Lopez & Caitlin Aamodt & Rob Knight & Nathan E. Lewis, 2022. "Context-aware deconvolution of cell–cell communication with Tensor-cell2cell," Nature Communications, Nature, vol. 13(1), pages 1-15, December.
    12. Yaping Liu & Sarah C. Reed & Christopher Lo & Atish D. Choudhury & Heather A. Parsons & Daniel G. Stover & Gavin Ha & Gregory Gydush & Justin Rhoades & Denisse Rotem & Samuel Freeman & David W. Katz &, 2024. "FinaleMe: Predicting DNA methylation by the fragmentation patterns of plasma cell-free DNA," Nature Communications, Nature, vol. 15(1), pages 1-9, December.
    13. Liujia Qian & Jianqing Zhu & Zhangzhi Xue & Yan Zhou & Nan Xiang & Hong Xu & Rui Sun & Wangang Gong & Xue Cai & Lu Sun & Weigang Ge & Yufeng Liu & Ying Su & Wangmin Lin & Yuecheng Zhan & Junjian Wang , 2024. "Proteomic landscape of epithelial ovarian cancer," Nature Communications, Nature, vol. 15(1), pages 1-20, December.
    14. Andrea Flesken-Nikitin & Coulter Q. Ralston & Dah-Jiun Fu & Andrea J. Micheli & Daryl J. Phuong & Blaine A. Harlan & Christopher S. Ashe & Amanda P. Armstrong & David W. McKellar & Sangeeta Ghuwalewal, 2024. "Pre-ciliated tubal epithelial cells are prone to initiation of high-grade serous ovarian carcinoma," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    15. Nicolette M. Fonseca & Corinne Maurice-Dror & Cameron Herberts & Wilson Tu & William Fan & Andrew J. Murtha & Catarina Kollmannsberger & Edmond M. Kwan & Karan Parekh & Elena Schönlau & Cecily Q. Bern, 2024. "Prediction of plasma ctDNA fraction and prognostic implications of liquid biopsy in advanced prostate cancer," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    16. Daniel Dimitrov & Dénes Türei & Martin Garrido-Rodriguez & Paul L. Burmedi & James S. Nagai & Charlotte Boys & Ricardo O. Ramirez Flores & Hyojin Kim & Bence Szalai & Ivan G. Costa & Alberto Valdeoliv, 2022. "Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data," Nature Communications, Nature, vol. 13(1), pages 1-13, December.
    17. Rongting Huang & Xianjie Huang & Yin Tong & Helen Y. N. Yan & Suet Yi Leung & Oliver Stegle & Yuanhua Huang, 2024. "Robust analysis of allele-specific copy number alterations from scRNA-seq data with XClone," Nature Communications, Nature, vol. 15(1), pages 1-16, December.
    18. Maja Marklund & Niklas Schultz & Stefanie Friedrich & Emelie Berglund & Firas Tarish & Anna Tanoglidi & Yao Liu & Ludvig Bergenstråhle & Andrew Erickson & Thomas Helleday & Alastair D. Lamb & Erik Son, 2022. "Spatio-temporal analysis of prostate tumors in situ suggests pre-existence of treatment-resistant clones," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    19. Alicia-Marie Conway & Simon P. Pearce & Alexandra Clipson & Steven M. Hill & Francesca Chemi & Dan Slane-Tan & Saba Ferdous & A. S. Md Mukarram Hossain & Katarzyna Kamieniecka & Daniel J. White & Clai, 2024. "A cfDNA methylation-based tissue-of-origin classifier for cancers of unknown primary," Nature Communications, Nature, vol. 15(1), pages 1-12, December.
    20. Xiao Zhou & Zhen Cheng & Mingyu Dong & Qi Liu & Weiyang Yang & Min Liu & Junzhang Tian & Weibin Cheng, 2022. "Tumor fractions deciphered from circulating cell-free DNA methylation for cancer early diagnosis," Nature Communications, Nature, vol. 13(1), pages 1-13, 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:15:y:2024:i:1:d:10.1038_s41467-024-47271-y. 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.