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Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers

Breast cancer is the most common cause of cancer death among women worldwide. Localized breast cancer can be cured by surgery and adjuvant therapy, but mortality remains high for tumors that metastasize early. Type IV collagen is a basement membrane protein, and breach of this extracellular matrix s...

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Autores principales: Jansson, Malin, Lindberg, Jessica, Rask, Gunilla, Svensson, Johan, Billing, Ola, Nazemroaya, Anoosheh, Berglund, Anette, Wärnberg, Fredrik, Sund, Malin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174894/
https://www.ncbi.nlm.nih.gov/pubmed/35693557
http://dx.doi.org/10.3389/fmolb.2022.904526
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author Jansson, Malin
Lindberg, Jessica
Rask, Gunilla
Svensson, Johan
Billing, Ola
Nazemroaya, Anoosheh
Berglund, Anette
Wärnberg, Fredrik
Sund, Malin
author_facet Jansson, Malin
Lindberg, Jessica
Rask, Gunilla
Svensson, Johan
Billing, Ola
Nazemroaya, Anoosheh
Berglund, Anette
Wärnberg, Fredrik
Sund, Malin
author_sort Jansson, Malin
collection PubMed
description Breast cancer is the most common cause of cancer death among women worldwide. Localized breast cancer can be cured by surgery and adjuvant therapy, but mortality remains high for tumors that metastasize early. Type IV collagen is a basement membrane protein, and breach of this extracellular matrix structure is the first step of cancer invasion. Type IV collagen is found in the stroma of many cancers, but its role in tumor biology is unclear. Here, expression of type IV collagen in the stroma of small breast cancers was analyzed, correlated to clinically used prognostic biomarkers and patient survival. The findings were further validated in an independent gene expression data cohort. Tissue samples from 1,379 women with in situ and small invasive breast cancers (≤15 mm) diagnosed in 1986-2004 were included. Primary tumor tissue was collected into tissue microarrays. Type IV collagen expression in tissues was visualized using immunohistochemistry. Gene expression data was extracted from the Cancer Genome Atlas database. Out of 1,379 women, 856 had an invasive breast cancer and type IV collagen staining was available for 714 patients. In Kaplan-Meier analysis high type IV collagen expression was significantly associated (p = 0.026) with poorer breast cancer specific survival. There was no correlation of type IV collagen expression to clinically used prognostic biomarkers. High type IV collagen expression was clearly associated to distant metastasis (p = 0.002). In an external validation cohort (n = 1,104), high type IV collagen mRNA expression was significantly (p = 0.041) associated with poorer overall survival, with overexpression of type IV collagen mRNA in metastatic tissue. Stromal type IV collagen expression in the primary tumor correlates to poor breast cancer specific survival most likely due to a higher risk of developing distant metastasis. This ECM protein may function as biomarker to predict the risk of future metastatic disease in patients with breast cancers.
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spelling pubmed-91748942022-06-09 Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers Jansson, Malin Lindberg, Jessica Rask, Gunilla Svensson, Johan Billing, Ola Nazemroaya, Anoosheh Berglund, Anette Wärnberg, Fredrik Sund, Malin Front Mol Biosci Molecular Biosciences Breast cancer is the most common cause of cancer death among women worldwide. Localized breast cancer can be cured by surgery and adjuvant therapy, but mortality remains high for tumors that metastasize early. Type IV collagen is a basement membrane protein, and breach of this extracellular matrix structure is the first step of cancer invasion. Type IV collagen is found in the stroma of many cancers, but its role in tumor biology is unclear. Here, expression of type IV collagen in the stroma of small breast cancers was analyzed, correlated to clinically used prognostic biomarkers and patient survival. The findings were further validated in an independent gene expression data cohort. Tissue samples from 1,379 women with in situ and small invasive breast cancers (≤15 mm) diagnosed in 1986-2004 were included. Primary tumor tissue was collected into tissue microarrays. Type IV collagen expression in tissues was visualized using immunohistochemistry. Gene expression data was extracted from the Cancer Genome Atlas database. Out of 1,379 women, 856 had an invasive breast cancer and type IV collagen staining was available for 714 patients. In Kaplan-Meier analysis high type IV collagen expression was significantly associated (p = 0.026) with poorer breast cancer specific survival. There was no correlation of type IV collagen expression to clinically used prognostic biomarkers. High type IV collagen expression was clearly associated to distant metastasis (p = 0.002). In an external validation cohort (n = 1,104), high type IV collagen mRNA expression was significantly (p = 0.041) associated with poorer overall survival, with overexpression of type IV collagen mRNA in metastatic tissue. Stromal type IV collagen expression in the primary tumor correlates to poor breast cancer specific survival most likely due to a higher risk of developing distant metastasis. This ECM protein may function as biomarker to predict the risk of future metastatic disease in patients with breast cancers. Frontiers Media S.A. 2022-05-25 /pmc/articles/PMC9174894/ /pubmed/35693557 http://dx.doi.org/10.3389/fmolb.2022.904526 Text en Copyright © 2022 Jansson, Lindberg, Rask, Svensson, Billing, Nazemroaya, Berglund, Wärnberg and Sund. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Biosciences
Jansson, Malin
Lindberg, Jessica
Rask, Gunilla
Svensson, Johan
Billing, Ola
Nazemroaya, Anoosheh
Berglund, Anette
Wärnberg, Fredrik
Sund, Malin
Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
title Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
title_full Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
title_fullStr Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
title_full_unstemmed Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
title_short Prognostic Value of Stromal Type IV Collagen Expression in Small Invasive Breast Cancers
title_sort prognostic value of stromal type iv collagen expression in small invasive breast cancers
topic Molecular Biosciences
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9174894/
https://www.ncbi.nlm.nih.gov/pubmed/35693557
http://dx.doi.org/10.3389/fmolb.2022.904526
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