{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T21:39:51Z","timestamp":1789767591132,"version":"4.0.1"},"reference-count":68,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2023,9,10]],"date-time":"2023-09-10T00:00:00Z","timestamp":1694304000000},"content-version":"vor","delay-in-days":9,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Clinical &amp; Translational Med"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>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.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we used single\u2010cell RNA\u2010sequencing to study the heterogeneity of 10 MPEs from seven metastatic breast cancer patients, including three Miltenyi\u2010enriched samples using a negative selection approach. This dataset of almost 65\u00a0000 cells was analysed using integrative approaches to compare heterogeneous cell populations and phenotypes.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We identified substantial inter\u2010patient heterogeneity in the composition of cell types (including malignant, mesothelial and immune cell populations), in expression of subtype\u2010specific 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\u2010associated fibroblast\u2010like transcriptomic program that may support cancer growth.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our dataset presents the first unbiased assessment of breast cancer\u2010associated 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.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ctm2.1356","type":"journal-article","created":{"date-parts":[[2023,9,11]],"date-time":"2023-09-11T05:55:48Z","timestamp":1694411748000},"source":"Crossref","is-referenced-by-count":12,"title":["Single\u2010cell RNA sequencing captures patient\u2010level heterogeneity and associated molecular phenotypes in breast cancer pleural effusions"],"prefix":"10.1002","volume":"13","author":[{"given":"Holly J.","family":"Whitfield","sequence":"first","affiliation":[{"name":"Department of Medical Biology, The Faculty of Medicine Dentistry and Health Science, The University of Melbourne Carlton Victoria Australia"},{"name":"Bioinformatics Division The Walter and Eliza Hall Institute of Medical Research Parkville Victoria 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