High Caveolin-1 mRNA expression in triple-negative breast cancer is associated with an aggressive tumor microenvironment, chemoresistance, and poor clinical outcome
(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.
(Less)
- author
- Godina, Christopher
LU
; Khazaei, Somayeh LU ; Belting, Mattias LU ; Vallon-Christersson, Johan LU
; Nodin, Björn LU ; Jirström, Karin LU
; Isaksson, Karolin LU ; Bosch, Ana LU and Jernström, Helena LU
- organization
-
- LUCC: Lund University Cancer Centre
- Cancerepidemiology and radiation
- Epidemiology and pharmacogenetics (research group)
- Tumor microenvironment (research group)
- Breastcancer-genetics
- Personalized Pathology & Cancer Therapy (research group)
- Therapeutic pathology
- Lund Melanoma Study Group (research group)
- EpiHealth: Epidemiology for Health
- publishing date
- 2024-07-03
- 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}}, }