Document Type
Journal Article
Publication Title
Nature Communications
Volume
15
Issue
1
PubMed ID
38570491
Publisher
Nature
School
Centre for Precision Health
RAS ID
65708
Funders
Cancer Council Western Australia / Cancer Research Trust / Australian Government / MACA Ride to Conquer Cancer / National Health and Medical Research Council / Government of Western Australia / Australian Cancer Research Foundation Centre for Advanced Cancer Genomics
Grant Number
NHMRC Numbers : APP1154524, APP2025225
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.
DOI
10.1038/s41467-024-47271-y
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Denisenko, E., de Kock, L., Tan, A., Beasley, A. B., Beilin, M., Jones, M. E., . . . Forrest, A. R. R. (2024). Spatial transcriptomics reveals discrete tumour microenvironments and autocrine loops within ovarian cancer subclones. Nature Communications, 15, article 2860. https://doi.org/10.1038/s41467-024-47271-y