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Protein profiling o...
Protein profiling of fine-needle aspirates reveals subtype-associated immune signatures and involvement of chemokines in breast cancer
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- Franzen, Bo (author)
- Karolinska Institutet
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- Alexeyenko, Andrey (author)
- Karolinska Institutet
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- Kamali-Moghaddam, Masood (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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- Hatschek, Thomas (author)
- Karolinska Institutet
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- Kanter, Lena (author)
- Karolinska Institutet
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- Ramqvist, Torbjorn (author)
- Karolinska Institutet
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- Kierkegaard, Jonas (author)
- BrostCtr City, Stockholm, Sweden;Capio St Gorans Sjukhus, Stockholm, Sweden
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- Masucci, Giuseppe (author)
- Karolinska Institutet
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- Auer, Gert (author)
- Karolinska Institutet
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- Landegren, Ulf (author)
- Uppsala universitet,Molekylära verktyg,Science for Life Laboratory, SciLifeLab
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- Lewensohn, Rolf (author)
- Karolinska Institutet
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(creator_code:org_t)
- 2019-01-07
- 2019
- English.
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In: Molecular Oncology. - : WILEY. - 1574-7891 .- 1878-0261. ; 13:2, s. 376-391
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Abstract
Subject headings
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- 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.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Cell- och molekylärbiologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Cell and Molecular Biology (hsv//eng)
Keyword
- breast cancer subtypes
- fibroadenomas
- fine-needle aspiration
- immune-related protein biomarker
- proximity extension assay
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Franzen, Bo
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Alexeyenko, Andr ...
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Kamali-Moghaddam ...
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Hatschek, Thomas
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Kanter, Lena
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Ramqvist, Torbjo ...
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show more...
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Kierkegaard, Jon ...
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Masucci, Giusepp ...
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Auer, Gert
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Landegren, Ulf
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Lewensohn, Rolf
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Cell and Molecul ...
- Articles in the publication
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Molecular Oncolo ...
- By the university
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Uppsala University
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Karolinska Institutet