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High Caveolin-1 mRNA expression in triple-negative breast cancer is associated with an aggressive tumor microenvironment, chemoresistance, and poor clinical outcome

Godina, Christopher LU orcid ; Khazaei, Somayeh LU ; Belting, Mattias LU ; Vallon-Christersson, Johan LU orcid ; Nodin, Björn LU ; Jirström, Karin LU orcid ; Isaksson, Karolin LU ; Bosch, Ana LU and Jernström, Helena LU (2024) In PLoS ONE 19(7). p.1-21
Abstract

BACKGROUND: Currently, there are few treatment-predictive and prognostic biomarkers in triple-negative breast cancer (TNBC). Caveolin-1 (CAV1) is linked to chemoresistance and several important processes involved in tumor progression and metastasis, such as epithelial-mesenchymal transition (EMT). Herein, we report that high CAV1 gene expression is an independent factor of poor prognosis in TNBC.

METHODS: CAV1 gene expression was compared across different molecular features (e.g., PAM50 subtypes). CAV1 expression was assessed in relation to clinical outcomes using Cox regression adjusted for clinicopathological predictors. Differential gene expression and gene set enrichment analyses were applied to compare high- and... (More)

BACKGROUND: Currently, there are few treatment-predictive and prognostic biomarkers in triple-negative breast cancer (TNBC). Caveolin-1 (CAV1) is linked to chemoresistance and several important processes involved in tumor progression and metastasis, such as epithelial-mesenchymal transition (EMT). Herein, we report that high CAV1 gene expression is an independent factor of poor prognosis in TNBC.

METHODS: CAV1 gene expression was compared across different molecular features (e.g., PAM50 subtypes). CAV1 expression was assessed in relation to clinical outcomes using Cox regression adjusted for clinicopathological predictors. Differential gene expression and gene set enrichment analyses were applied to compare high- and low-expressing CAV1 tumors. Tumor microenvironment composition of high- and low-expressing CAV1 tumors was estimated using ECOTYPER. Tumor tissue microarrays were used to evaluate CAV1 protein levels in stromal and malignant cells.

RESULTS: In the SCAN-B (n = 525) and GSE31519 (n = 327) cohorts, patients with CAV1-high tumors had an increased incidence of early recurrence adjusted HR 1.78 (95% CI 1.12-2.81) and 2.20 (95% CI 1.39-3.47), respectively. In further analysis, high CAV1 gene expression was associated with a molecular profile indicating altered metabolism, neovascularization, chemoresistance, EMT, suppressed immune response, and active tumor microenvironment. Protein levels of CAV1 in malignant and stromal cells were not correlated with CAV1 gene expression.

CONCLUSION: CAV1 gene expression in TNBC is a biomarker that merits further investigation in clinical trials and as a therapeutic target.

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author
; ; ; ; ; ; ; and
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Humans, Caveolin 1/genetics, Triple Negative Breast Neoplasms/genetics, Tumor Microenvironment/genetics, Female, Drug Resistance, Neoplasm/genetics, Middle Aged, Gene Expression Regulation, Neoplastic, RNA, Messenger/genetics, Prognosis, Biomarkers, Tumor/genetics, Epithelial-Mesenchymal Transition/genetics, Aged
in
PLoS ONE
volume
19
issue
7
article number
e0305222
pages
1 - 21
publisher
Public Library of Science (PLoS)
external identifiers
  • pmid:38959243
ISSN
1932-6203
DOI
10.1371/journal.pone.0305222
language
English
LU publication?
yes
additional info
Copyright: © 2024 Godina et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
id
326896bc-10d0-46cb-a570-2f8e5ced9ef1
date added to LUP
2024-07-04 17:19:21
date last changed
2024-07-05 06:53:38
@article{326896bc-10d0-46cb-a570-2f8e5ced9ef1,
  abstract     = {{<p>BACKGROUND: Currently, there are few treatment-predictive and prognostic biomarkers in triple-negative breast cancer (TNBC). Caveolin-1 (CAV1) is linked to chemoresistance and several important processes involved in tumor progression and metastasis, such as epithelial-mesenchymal transition (EMT). Herein, we report that high CAV1 gene expression is an independent factor of poor prognosis in TNBC.</p><p>METHODS: CAV1 gene expression was compared across different molecular features (e.g., PAM50 subtypes). CAV1 expression was assessed in relation to clinical outcomes using Cox regression adjusted for clinicopathological predictors. Differential gene expression and gene set enrichment analyses were applied to compare high- and low-expressing CAV1 tumors. Tumor microenvironment composition of high- and low-expressing CAV1 tumors was estimated using ECOTYPER. Tumor tissue microarrays were used to evaluate CAV1 protein levels in stromal and malignant cells.</p><p>RESULTS: In the SCAN-B (n = 525) and GSE31519 (n = 327) cohorts, patients with CAV1-high tumors had an increased incidence of early recurrence adjusted HR 1.78 (95% CI 1.12-2.81) and 2.20 (95% CI 1.39-3.47), respectively. In further analysis, high CAV1 gene expression was associated with a molecular profile indicating altered metabolism, neovascularization, chemoresistance, EMT, suppressed immune response, and active tumor microenvironment. Protein levels of CAV1 in malignant and stromal cells were not correlated with CAV1 gene expression.</p><p>CONCLUSION: CAV1 gene expression in TNBC is a biomarker that merits further investigation in clinical trials and as a therapeutic target.</p>}},
  author       = {{Godina, Christopher and Khazaei, Somayeh and Belting, Mattias and Vallon-Christersson, Johan and Nodin, Björn and Jirström, Karin and Isaksson, Karolin and Bosch, Ana and Jernström, Helena}},
  issn         = {{1932-6203}},
  keywords     = {{Humans; Caveolin 1/genetics; Triple Negative Breast Neoplasms/genetics; Tumor Microenvironment/genetics; Female; Drug Resistance, Neoplasm/genetics; Middle Aged; Gene Expression Regulation, Neoplastic; RNA, Messenger/genetics; Prognosis; Biomarkers, Tumor/genetics; Epithelial-Mesenchymal Transition/genetics; Aged}},
  language     = {{eng}},
  month        = {{07}},
  number       = {{7}},
  pages        = {{1--21}},
  publisher    = {{Public Library of Science (PLoS)}},
  series       = {{PLoS ONE}},
  title        = {{High Caveolin-1 mRNA expression in triple-negative breast cancer is associated with an aggressive tumor microenvironment, chemoresistance, and poor clinical outcome}},
  url          = {{http://dx.doi.org/10.1371/journal.pone.0305222}},
  doi          = {{10.1371/journal.pone.0305222}},
  volume       = {{19}},
  year         = {{2024}},
}