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Interplay between Caveolin-1 and body and tumor size affects clinical outcomes in breast cancer

Godina, Christopher LU orcid ; Indira Chandran, Vineesh LU ; Barbachowska, Magdalena LU ; Tryggvadottir, Helga LU ; Nodin, Björn LU ; Visse, Edward LU ; Borgquist, Signe LU ; Jirström, Karin LU orcid ; Isaksson, Karolin LU and Bosch, Ana LU , et al. (2022) In Translational Oncology 22.
Abstract

BACKGROUND: Caveolin-1 (CAV1) is associated with cholesterol-rich membrane raft domains and is a master regulator of cell signaling and membrane transport. Here, we investigated CAV1's role in cellular compartments of breast cancer in relation to signaling pathways, clinicopathological features, and clinical outcomes.

METHODS: CAV1 levels were evaluated with immunohistochemistry in cytoplasm of invasive tumor cells and stromal cells in tumor tissue microarrays from a cohort of 1018 breast cancer patients (inclusion 2002-2012, Sweden). Cytoplasmic and stromal CAV1 were categorized as positive/negative and strong/not strong, respectively. CAV1 expression in relation to clinical outcomes was assessed with Cox regression.... (More)

BACKGROUND: Caveolin-1 (CAV1) is associated with cholesterol-rich membrane raft domains and is a master regulator of cell signaling and membrane transport. Here, we investigated CAV1's role in cellular compartments of breast cancer in relation to signaling pathways, clinicopathological features, and clinical outcomes.

METHODS: CAV1 levels were evaluated with immunohistochemistry in cytoplasm of invasive tumor cells and stromal cells in tumor tissue microarrays from a cohort of 1018 breast cancer patients (inclusion 2002-2012, Sweden). Cytoplasmic and stromal CAV1 were categorized as positive/negative and strong/not strong, respectively. CAV1 expression in relation to clinical outcomes was assessed with Cox regression. Investigations into CAV1 functional pathways was conducted in the STRING, GOBO, and TCGA databases.

RESULTS: CAV1 expression was associated with non-luminal subtypes, cell cycle control, inflammation, epithelial-mesenchymal transition, and the IGF/Insulin system. Generally, CAV1 was not associated with recurrence risk. Stromal CAV1's impact on recurrence risk was modified by BMI ≥25 kg/m2 (Pinteraction = 0.002), waist ≥80 cm (Pinteraction = 0.005), and invasive tumor size (pT2/3/4) (Pinteraction = 0.028). In low-risk patients only, strong stromal CAV1 significantly increased recurrence risk (HRsadj ≥1.61). In all patients, positive cytoplasmic CAV1 conferred >2-fold risk for contralateral disease HRadj 2.63 (95% CI 1.36-5.10). Strong stromal CAV1 conferred nearly 2-fold risk for locoregional recurrence HRadj 1.88 (95% CI 1.09-3.24).

CONCLUSIONS: CAV1's prognostic impact depended on its localization, anthropometric, and tumor factors. Stromal CAV1 predicted high recurrence risk in a group of supposedly 'low-risk' patients. Cytoplasmic CAV1 predicted metachronous contralateral disease. If confirmed, CAV1 could be used as treatment target and for risk-stratification.

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organization
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type
Contribution to journal
publication status
published
subject
in
Translational Oncology
volume
22
article number
101464
publisher
Neoplasia Press
external identifiers
  • pmid:35660849
  • scopus:85131414822
ISSN
1936-5233
DOI
10.1016/j.tranon.2022.101464
language
English
LU publication?
yes
id
e9ac955e-a2e3-4371-9a44-a806e42b8d75
date added to LUP
2022-08-29 08:56:42
date last changed
2024-06-14 21:13:45
@article{e9ac955e-a2e3-4371-9a44-a806e42b8d75,
  abstract     = {{<p>BACKGROUND: Caveolin-1 (CAV1) is associated with cholesterol-rich membrane raft domains and is a master regulator of cell signaling and membrane transport. Here, we investigated CAV1's role in cellular compartments of breast cancer in relation to signaling pathways, clinicopathological features, and clinical outcomes.</p><p>METHODS: CAV1 levels were evaluated with immunohistochemistry in cytoplasm of invasive tumor cells and stromal cells in tumor tissue microarrays from a cohort of 1018 breast cancer patients (inclusion 2002-2012, Sweden). Cytoplasmic and stromal CAV1 were categorized as positive/negative and strong/not strong, respectively. CAV1 expression in relation to clinical outcomes was assessed with Cox regression. Investigations into CAV1 functional pathways was conducted in the STRING, GOBO, and TCGA databases.</p><p>RESULTS: CAV1 expression was associated with non-luminal subtypes, cell cycle control, inflammation, epithelial-mesenchymal transition, and the IGF/Insulin system. Generally, CAV1 was not associated with recurrence risk. Stromal CAV1's impact on recurrence risk was modified by BMI ≥25 kg/m2 (Pinteraction = 0.002), waist ≥80 cm (Pinteraction = 0.005), and invasive tumor size (pT2/3/4) (Pinteraction = 0.028). In low-risk patients only, strong stromal CAV1 significantly increased recurrence risk (HRsadj ≥1.61). In all patients, positive cytoplasmic CAV1 conferred &gt;2-fold risk for contralateral disease HRadj 2.63 (95% CI 1.36-5.10). Strong stromal CAV1 conferred nearly 2-fold risk for locoregional recurrence HRadj 1.88 (95% CI 1.09-3.24).</p><p>CONCLUSIONS: CAV1's prognostic impact depended on its localization, anthropometric, and tumor factors. Stromal CAV1 predicted high recurrence risk in a group of supposedly 'low-risk' patients. Cytoplasmic CAV1 predicted metachronous contralateral disease. If confirmed, CAV1 could be used as treatment target and for risk-stratification.</p>}},
  author       = {{Godina, Christopher and Indira Chandran, Vineesh and Barbachowska, Magdalena and Tryggvadottir, Helga and Nodin, Björn and Visse, Edward and Borgquist, Signe and Jirström, Karin and Isaksson, Karolin and Bosch, Ana and Belting, Mattias and Jernström, Helena}},
  issn         = {{1936-5233}},
  language     = {{eng}},
  publisher    = {{Neoplasia Press}},
  series       = {{Translational Oncology}},
  title        = {{Interplay between Caveolin-1 and body and tumor size affects clinical outcomes in breast cancer}},
  url          = {{http://dx.doi.org/10.1016/j.tranon.2022.101464}},
  doi          = {{10.1016/j.tranon.2022.101464}},
  volume       = {{22}},
  year         = {{2022}},
}