Caveolin-1 gene expression provides additional prognostic information combined with PAM50 risk of recurrence (ROR) score in breast cancer
(2024) In Scientific Reports 14(1).- Abstract
Combining information from the tumor microenvironment (TME) with PAM50 Risk of Recurrence (ROR) score could improve breast cancer prognostication. Caveolin-1 (CAV1) is a marker of an active TME. CAV1 is a membrane protein involved in cell signaling, extracellular matrix organization, and tumor-stroma interactions. We sought to investigate CAV1 gene expression in relation to PAM50 subtypes, ROR score, and their joint prognostic impact. CAV1 expression was compared between PAM50 subtypes and ROR categories in two cohorts (SCAN-B, n = 5326 and METABRIC, n = 1980). CAV1 expression was assessed in relation to clinical outcomes using Cox regression and adjusted for clinicopathological predictors. Effect modifications between CAV1 expression... (More)
Combining information from the tumor microenvironment (TME) with PAM50 Risk of Recurrence (ROR) score could improve breast cancer prognostication. Caveolin-1 (CAV1) is a marker of an active TME. CAV1 is a membrane protein involved in cell signaling, extracellular matrix organization, and tumor-stroma interactions. We sought to investigate CAV1 gene expression in relation to PAM50 subtypes, ROR score, and their joint prognostic impact. CAV1 expression was compared between PAM50 subtypes and ROR categories in two cohorts (SCAN-B, n = 5326 and METABRIC, n = 1980). CAV1 expression was assessed in relation to clinical outcomes using Cox regression and adjusted for clinicopathological predictors. Effect modifications between CAV1 expression and ROR categories on clinical outcome were investigated using multiplicative and additive two-way interaction analyses. Differential gene expression and gene set enrichment analyses were applied to compare high and low expressing CAV1 tumors. All samples expressed CAV1 with the highest expression in the Normal-like subtype. Gene modules consistent with epithelial-mesenchymal transition (EMT), hypoxia, and stromal activation were associated with high CAV1 expression. CAV1 expression was inversely associated with ROR category. Interactions between CAV1 expression and ROR categories were observed in both cohorts. High expressing CAV1 tumors conferred worse prognosis only within the group classified as ROR high. ROR gave markedly different prognostic information depending on the underlying CAV1 expression. CAV1, a potential mediator between the malignant cells and TME, could be a useful biomarker that enhances and further refines PAM50 ROR risk stratification in patients with ROR high tumors and a potential therapeutic target.
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- author
- Godina, Christopher LU ; Belting, Mattias LU ; Vallon-Christersson, Johan LU ; Isaksson, Karolin LU ; Bosch, Ana LU and Jernström, Helena LU
- organization
-
- LUCC: Lund University Cancer Centre
- Cancerepidemiology and radiation
- Tumor microenvironment (research group)
- Tumor microenvironment
- Breastcancer-genetics
- Lund Melanoma Study Group (research group)
- Molecular therapeutics in breast cancer (research group)
- EpiHealth: Epidemiology for Health
- Epidemiology and pharmacogenetics (research group)
- publishing date
- 2024-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Breast cancer, Caveolin-1, Molecular profiling, PAM50 ROR, Prognostic markers
- in
- Scientific Reports
- volume
- 14
- issue
- 1
- article number
- 6675
- publisher
- Nature Publishing Group
- external identifiers
-
- pmid:38509243
- scopus:85188150614
- ISSN
- 2045-2322
- DOI
- 10.1038/s41598-024-57365-8
- language
- English
- LU publication?
- yes
- id
- 0ebf98f3-b2fd-4a03-bc0b-751c9b94fca4
- date added to LUP
- 2024-04-04 08:50:10
- date last changed
- 2024-05-16 13:27:37
@article{0ebf98f3-b2fd-4a03-bc0b-751c9b94fca4, abstract = {{<p>Combining information from the tumor microenvironment (TME) with PAM50 Risk of Recurrence (ROR) score could improve breast cancer prognostication. Caveolin-1 (CAV1) is a marker of an active TME. CAV1 is a membrane protein involved in cell signaling, extracellular matrix organization, and tumor-stroma interactions. We sought to investigate CAV1 gene expression in relation to PAM50 subtypes, ROR score, and their joint prognostic impact. CAV1 expression was compared between PAM50 subtypes and ROR categories in two cohorts (SCAN-B, n = 5326 and METABRIC, n = 1980). CAV1 expression was assessed in relation to clinical outcomes using Cox regression and adjusted for clinicopathological predictors. Effect modifications between CAV1 expression and ROR categories on clinical outcome were investigated using multiplicative and additive two-way interaction analyses. Differential gene expression and gene set enrichment analyses were applied to compare high and low expressing CAV1 tumors. All samples expressed CAV1 with the highest expression in the Normal-like subtype. Gene modules consistent with epithelial-mesenchymal transition (EMT), hypoxia, and stromal activation were associated with high CAV1 expression. CAV1 expression was inversely associated with ROR category. Interactions between CAV1 expression and ROR categories were observed in both cohorts. High expressing CAV1 tumors conferred worse prognosis only within the group classified as ROR high. ROR gave markedly different prognostic information depending on the underlying CAV1 expression. CAV1, a potential mediator between the malignant cells and TME, could be a useful biomarker that enhances and further refines PAM50 ROR risk stratification in patients with ROR high tumors and a potential therapeutic target.</p>}}, author = {{Godina, Christopher and Belting, Mattias and Vallon-Christersson, Johan and Isaksson, Karolin and Bosch, Ana and Jernström, Helena}}, issn = {{2045-2322}}, keywords = {{Breast cancer; Caveolin-1; Molecular profiling; PAM50 ROR; Prognostic markers}}, language = {{eng}}, number = {{1}}, publisher = {{Nature Publishing Group}}, series = {{Scientific Reports}}, title = {{Caveolin-1 gene expression provides additional prognostic information combined with PAM50 risk of recurrence (ROR) score in breast cancer}}, url = {{http://dx.doi.org/10.1038/s41598-024-57365-8}}, doi = {{10.1038/s41598-024-57365-8}}, volume = {{14}}, year = {{2024}}, }