Please use this identifier to cite or link to this item: https://ahro.austin.org.au/austinjspui/handle/1/33772
Title: Single-cell RNA sequencing captures patient-level heterogeneity and associated molecular phenotypes in breast cancer pleural effusions.
Austin Authors: Whitfield, Holly J;Berthelet, Jean;Mangiola, Stefano;Bell, Caroline;Anderson, Robin L ;Pal, Bhupinder;Yeo, Belinda ;Papenfuss, Anthony T;Merino, Delphine;Davis, Melissa J
Affiliation: Department of Medical Biology, The Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Carlton, Victoria, Australia.
Olivia Newton-John Cancer Research Institute
Department of Medical Biology, The Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Carlton, Victoria, Australia.
School of Cancer Medicine, La Trobe University, Bundoora, Victoria, Australia.
Peter MacCallum Cancer Centre, Parkville, Victoria, Australia.
Department of Clinical Pathology, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Carlton, Victoria, Australia.
Bioinformatics Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.;Department of Clinical Pathology, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Carlton, Victoria, Australia.;Sir Peter MacCallum Department of Oncology, The University of Melbourne, Carlton, Victoria, Australia.
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria, Australia.
Department of Clinical Pathology, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Carlton, Victoria, Australia.;The University of Queensland Diamantina Institute, The University of Queensland, Brisbane, Queensland, Australia.;The South Australian Immunogenomics Cancer Institute, The University of Adelaide, Adelaide, South Australia, Australia.
Issue Date: Sep-2023
Publication information: Clinical and Translational Medicine 2023-09; 13(9)
Abstract: Malignant pleural effusions (MPEs) are a common complication of advanced cancers, particularly those adjacent to the pleura, such as lung and breast cancer. The pathophysiology of MPE formation remains poorly understood, and although MPEs are routinely used for the diagnosis of breast cancer patients, their composition and biology are poorly understood. It is difficult to distinguish invading malignant cells from resident mesothelial cells and to identify the directionality of interactions between these populations in the pleura. There is a need to characterize the phenotypic diversity of breast cancer cell populations in the pleural microenvironment, and investigate how this varies across patients. Here, we used single-cell RNA-sequencing to study the heterogeneity of 10 MPEs from seven metastatic breast cancer patients, including three Miltenyi-enriched samples using a negative selection approach. This dataset of almost 65 000 cells was analysed using integrative approaches to compare heterogeneous cell populations and phenotypes. We identified substantial inter-patient heterogeneity in the composition of cell types (including malignant, mesothelial and immune cell populations), in expression of subtype-specific gene signatures and in copy number aberration patterns, that captured variability across breast cancer cell populations. Within individual MPEs, we distinguished mesothelial cell populations from malignant cells using key markers, the presence of breast cancer subtype expression patterns and copy number aberration patterns. We also identified pleural mesothelial cells expressing a cancer-associated fibroblast-like transcriptomic program that may support cancer growth. Our dataset presents the first unbiased assessment of breast cancer-associated MPEs at a single cell resolution, providing the community with a valuable resource for the study of MPEs. Our work highlights the molecular and cellular diversity captured in MPEs and motivates the potential use of these clinically relevant biopsies in the development of targeted therapeutics for patients with advanced breast cancer.
URI: https://ahro.austin.org.au/austinjspui/handle/1/33772
DOI: 10.1002/ctm2.1356
ORCID: 0000-0003-2562-0575
0000-0002-8075-6275
Journal: Clinical and Translational Medicine
Start page: e1356
PubMed URL: 37691350
ISSN: 2001-1326
Type: Journal Article
Subjects: Breast Neoplasms/genetics
Tumor Microenvironment/genetics
Appears in Collections:Journal articles

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