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

Autor: Godina C; Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden., Khazaei S; Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden., Belting M; Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden.; Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Sweden.; Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden., Vallon-Christersson J; Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden., Nodin B; Department of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University, Lund, Sweden., Jirström K; Department of Clinical Sciences Lund, Oncology and Therapeutic Pathology, Lund University, Lund, Sweden., Isaksson K; Department of Clinical Sciences Lund, Surgery, Lund University and Kristianstad Hospital, Kristianstad, Sweden., Bosch A; Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden.; Department of Hematology, Oncology and Radiation Physics, Skåne University Hospital, Sweden., Jernström H; Department of Clinical Sciences Lund, Oncology, Lund University and Skåne University Hospital, Lund, Sweden.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2024 Jul 03; Vol. 19 (7), pp. e0305222. Date of Electronic Publication: 2024 Jul 03 (Print Publication: 2024).
DOI: 10.1371/journal.pone.0305222
Abstrakt: 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.
Competing Interests: Ana Bosch has received institutional honoraria from Pfizer, Roche and Lilly for consultation and lectures. She has participated in Advisory Board meetings for Pfizer and Novartis. Co-founder and chair of the board for SACRA therapeutics. Karolin Isaksson has received speaker honorarium from Pierre Fabre. The other authors declare no conflict of interest.
(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.)
Databáze: MEDLINE
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