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Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer
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;...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360506/ https://www.ncbi.nlm.nih.gov/pubmed/30451357 http://dx.doi.org/10.1002/1878-0261.12410 |
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author | Franzén, Bo Alexeyenko, Andrey Kamali‐Moghaddam, Masood Hatschek, Thomas Kanter, Lena Ramqvist, Torbjörn Kierkegaard, Jonas Masucci, Giuseppe Auer, Gert Landegren, Ulf Lewensohn, Rolf |
author_facet | Franzén, Bo Alexeyenko, Andrey Kamali‐Moghaddam, Masood Hatschek, Thomas Kanter, Lena Ramqvist, Torbjörn Kierkegaard, Jonas Masucci, Giuseppe Auer, Gert Landegren, Ulf Lewensohn, Rolf |
author_sort | Franzén, Bo |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6360506 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-63605062019-02-14 Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer Franzén, Bo Alexeyenko, Andrey Kamali‐Moghaddam, Masood Hatschek, Thomas Kanter, Lena Ramqvist, Torbjörn Kierkegaard, Jonas Masucci, Giuseppe Auer, Gert Landegren, Ulf Lewensohn, Rolf Mol Oncol Research Articles 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. John Wiley and Sons Inc. 2019-01-07 2019-02 /pmc/articles/PMC6360506/ /pubmed/30451357 http://dx.doi.org/10.1002/1878-0261.12410 Text en © 2018 The Authors. Published by FEBS Press and John Wiley & Sons Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Franzén, Bo Alexeyenko, Andrey Kamali‐Moghaddam, Masood Hatschek, Thomas Kanter, Lena Ramqvist, Torbjörn Kierkegaard, Jonas Masucci, Giuseppe Auer, Gert Landegren, Ulf Lewensohn, Rolf Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer |
title | Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer |
title_full | Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer |
title_fullStr | Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer |
title_full_unstemmed | Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer |
title_short | Protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer |
title_sort | protein profiling of fine‐needle aspirates reveals subtype‐associated immune signatures and involvement of chemokines in breast cancer |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6360506/ https://www.ncbi.nlm.nih.gov/pubmed/30451357 http://dx.doi.org/10.1002/1878-0261.12410 |
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