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Protein profiling of fine-needle aspirates reveals subtype-associated immune signatures and involvement of chemokines in breast cancer
Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, Z5 02, S-17176 Stockholm, Sweden;Univ Hosp, S-17176 Stockholm, Sweden.
Karolinska Inst, Dept Microbiol Tumor & Cell Biol MTC, Stockholm, Sweden;Natl Bioinformat Infrastruct Sweden, Sci Life Lab, Solna, Sweden.ORCID iD: 0000-0001-8812-6481
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular tools. Uppsala University, Science for Life Laboratory, SciLifeLab.ORCID iD: 0000-0002-1303-2218
Karolinska Inst, Dept Pathol & Oncol, Canc Ctr Karolinska, Z5 02, S-17176 Stockholm, Sweden;Univ Hosp, S-17176 Stockholm, Sweden;Karolinska Univ Hosp, Theme Canc Patient Area Head & Neck Lung & Skin, Stockholm, Sweden.
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2019 (English)In: Molecular Oncology, ISSN 1574-7891, E-ISSN 1878-0261, Vol. 13, no 2, p. 376-391Article in journal (Refereed) Published
Abstract [en]

There are increasing demands for informative cancer biomarkers, accessible via minimally invasive procedures, both for initial diagnostics and for follow-up of personalized cancer therapy, including immunotherapy. Fine-needle aspiration (FNA) biopsy provides ready access to relevant tissue samples; however, the minute amounts of sample require sensitive multiplex molecular analysis to be of clinical biomarker utility. We have applied proximity extension assays (PEA) to analyze 167 proteins in FNA samples from patients with breast cancer (BC; n = 25) and benign lesions (n = 32). We demonstrate that the FNA BC samples could be divided into two main clusters, characterized by differences in expression levels of the estrogen receptor (ER) and the proliferation marker Ki67. This clustering corresponded to some extent to established BC subtypes. Our analysis also revealed several proteins whose expression levels differed between BC and benign lesions (e.g., CA9, GZMB, IL-6, VEGFA, CXCL11, PDL1, and PCD1), as well as several chemokines correlating with ER and Ki67 status (e.g., CCL4, CCL8, CCL20, CXCL8, CXCL9, and CXCL17). Finally, we also identified three signatures that could predict Ki67 status, ER status, and tumor grade, respectively, based on a small subset of proteins, which was dominated by chemokines. To our knowledge, expression profiles of CCL13 in benign lesions and BC have not previously been described but were shown herein to correlate with proliferation (P = 0.00095), suggesting a role in advanced BC. Given the broad functional range of the proteins analyzed, immune-related proteins were overrepresented among the observed alterations. Our pilot study supports the emerging role of chemokines in BC progression. Due to the minimally traumatic sampling and clinically important molecular information for therapeutic decisions, this methodology is promising for future immunoscoring and monitoring of treatment efficacy in BC.

Place, publisher, year, edition, pages
WILEY , 2019. Vol. 13, no 2, p. 376-391
Keywords [en]
breast cancer subtypes, fibroadenomas, fine-needle aspiration, immune-related protein biomarker, proximity extension assay
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
URN: urn:nbn:se:uu:diva-377673DOI: 10.1002/1878-0261.12410ISI: 000457747900016PubMedID: 30451357OAI: oai:DiVA.org:uu-377673DiVA, id: diva2:1291545
Funder
VINNOVA, 2016-00595Swedish Foundation for Strategic Research Swedish Research CouncilEU, FP7, Seventh Framework Programme, 316929EU, FP7, Seventh Framework Programme, 294409Stockholm County Council, 20151043Stockholm County Council, 20160287Swedish Cancer Society, 170246Swedish Foundation for Strategic Research The Breast Cancer FoundationAvailable from: 2019-02-25 Created: 2019-02-25 Last updated: 2019-02-25Bibliographically approved

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