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Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer

BACKGROUND: Obesity induces molecular changes that may favor tumor progression and metastatic spread, leading to impaired survival outcomes in breast cancer. Adenylate cyclase-associated protein 1 (CAP1), an actin regulatory protein and functional receptor for the obesity-associated adipokine resist...

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Autores principales: Bergqvist, Malin, Elebro, Karin, Sandsveden, Malte, Borgquist, Signe, Rosendahl, Ann H.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304201/
https://www.ncbi.nlm.nih.gov/pubmed/32560703
http://dx.doi.org/10.1186/s13058-020-01307-5
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author Bergqvist, Malin
Elebro, Karin
Sandsveden, Malte
Borgquist, Signe
Rosendahl, Ann H.
author_facet Bergqvist, Malin
Elebro, Karin
Sandsveden, Malte
Borgquist, Signe
Rosendahl, Ann H.
author_sort Bergqvist, Malin
collection PubMed
description BACKGROUND: Obesity induces molecular changes that may favor tumor progression and metastatic spread, leading to impaired survival outcomes in breast cancer. Adenylate cyclase-associated protein 1 (CAP1), an actin regulatory protein and functional receptor for the obesity-associated adipokine resistin, has been implicated with inferior cancer prognosis. Here, the objective was to investigate the interplay between body composition and CAP1 tumor expression regarding breast cancer outcome through long-term survival analyses. METHODS: Among 718 women with primary invasive breast cancer within the large population-based prospective Malmö Diet and Cancer Study, tumor-specific CAP1 levels were assessed following thorough antibody validation and immunohistochemical staining of tumor tissue microarrays. Antibody specificity and functional application validity were determined by CAP1 gene silencing, qRT-PCR, Western immunoblotting, and cell microarray immunostaining. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of breast cancer-specific survival (BCSS) and overall survival (OS) according to body composition and CAP1 expression. RESULTS: Study participants were followed for up to 25 years (median 10.9 years), during which 239 deaths were observed. Patients with low CAP1 tumor expression were older at diagnosis, displayed anthropometric measurements indicating a higher adiposity status (wider waist and hip, higher body mass index and body fat percentage), and were more prone to have unfavorable tumor characteristics (higher histological grade, higher Ki67, and estrogen receptor (ER) negativity). Overall, patients with CAP1-low tumors had impaired BCSS (adjusted hazard ratio: HR(adj) = 0.52, 95% CI 0.31–0.88) and OS (HR(adj) = 0.64, 95% CI 0.44–0.92) compared with patients having high CAP1 tumor expression. Further, analyses stratified according to different anthropometric measures or ER status showed that the CAP1-associated survival outcomes were most pronounced among patients with low adiposity status or ER-positive disease. CONCLUSIONS: Low CAP1 tumor expression was associated with higher body fatness and worse survival outcomes in breast cancer patients with effect modification by adiposity and ER status. CAP1 could be a novel marker for poorer survival outcome in leaner or ER-positive breast cancer patients, highlighting the need for considering body constitution in clinical decision making.
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spelling pubmed-73042012020-06-22 Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer Bergqvist, Malin Elebro, Karin Sandsveden, Malte Borgquist, Signe Rosendahl, Ann H. Breast Cancer Res Research Article BACKGROUND: Obesity induces molecular changes that may favor tumor progression and metastatic spread, leading to impaired survival outcomes in breast cancer. Adenylate cyclase-associated protein 1 (CAP1), an actin regulatory protein and functional receptor for the obesity-associated adipokine resistin, has been implicated with inferior cancer prognosis. Here, the objective was to investigate the interplay between body composition and CAP1 tumor expression regarding breast cancer outcome through long-term survival analyses. METHODS: Among 718 women with primary invasive breast cancer within the large population-based prospective Malmö Diet and Cancer Study, tumor-specific CAP1 levels were assessed following thorough antibody validation and immunohistochemical staining of tumor tissue microarrays. Antibody specificity and functional application validity were determined by CAP1 gene silencing, qRT-PCR, Western immunoblotting, and cell microarray immunostaining. Kaplan-Meier and multivariable Cox proportional hazard models were used to assess survival differences in terms of breast cancer-specific survival (BCSS) and overall survival (OS) according to body composition and CAP1 expression. RESULTS: Study participants were followed for up to 25 years (median 10.9 years), during which 239 deaths were observed. Patients with low CAP1 tumor expression were older at diagnosis, displayed anthropometric measurements indicating a higher adiposity status (wider waist and hip, higher body mass index and body fat percentage), and were more prone to have unfavorable tumor characteristics (higher histological grade, higher Ki67, and estrogen receptor (ER) negativity). Overall, patients with CAP1-low tumors had impaired BCSS (adjusted hazard ratio: HR(adj) = 0.52, 95% CI 0.31–0.88) and OS (HR(adj) = 0.64, 95% CI 0.44–0.92) compared with patients having high CAP1 tumor expression. Further, analyses stratified according to different anthropometric measures or ER status showed that the CAP1-associated survival outcomes were most pronounced among patients with low adiposity status or ER-positive disease. CONCLUSIONS: Low CAP1 tumor expression was associated with higher body fatness and worse survival outcomes in breast cancer patients with effect modification by adiposity and ER status. CAP1 could be a novel marker for poorer survival outcome in leaner or ER-positive breast cancer patients, highlighting the need for considering body constitution in clinical decision making. BioMed Central 2020-06-19 2020 /pmc/articles/PMC7304201/ /pubmed/32560703 http://dx.doi.org/10.1186/s13058-020-01307-5 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research Article
Bergqvist, Malin
Elebro, Karin
Sandsveden, Malte
Borgquist, Signe
Rosendahl, Ann H.
Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer
title Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer
title_full Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer
title_fullStr Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer
title_full_unstemmed Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer
title_short Effects of tumor-specific CAP1 expression and body constitution on clinical outcomes in patients with early breast cancer
title_sort effects of tumor-specific cap1 expression and body constitution on clinical outcomes in patients with early breast cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7304201/
https://www.ncbi.nlm.nih.gov/pubmed/32560703
http://dx.doi.org/10.1186/s13058-020-01307-5
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