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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
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    References listed on IDEAS

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