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

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 P. W. Hmon, Yen Yeow, Youngmi Kim, Rhea John, Tami S. Gilderman, Emily Killingbeck, Elin S. Gray, Paul A. Cohen (), Yu Yu () and Alistair R. R. Forrest ()
Additional contact information
Elena Denisenko: The University of Western Australia, Nedlands
Leanne Kock: The University of Western Australia, Nedlands
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
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
Yu Yu: University of Western Australia
Alistair R. R. Forrest: The University of Western Australia, Nedlands

Nature Communications, 2024, vol. 15, issue 1, 1-15

Abstract: 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-47271-y Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47271-y

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-47271-y

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().