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

Godina, Christopher; Chandran, Vineesh Indira; Barbachowska, Magdalena; Tryggvadottir, Helga; Nodin, Björn; Visse, Edward; Borgquist, Signe; Jirström, Karin; Isaksson, Karolin; Bosch, Ana; Belting, Mattias; Jernström, Helena

doi:10.1016/j.tranon.2022.101464

Cited by 5 publications

(17 citation statements)

References 52 publications

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“…For patients with missing HER2 status, HER2 status was obtained from dual gene protein staining of HER2 on tissue microarrays, which showed 97.7% agreement with available pathological assessment [30]. Tumor-specific CAV1 staining was obtained and dichotomized, as previously described, into positive/negative for malignant cells and strong/not strong for stromal cells [13,31]. Anthropometric measurements were dichotomized as in the previous study [13].…”

Section: Cohort Descriptionmentioning

confidence: 99%

“…Tumor-specific CAV1 staining was obtained and dichotomized, as previously described, into positive/negative for malignant cells and strong/not strong for stromal cells [13,31]. Anthropometric measurements were dichotomized as in the previous study [13].…”

Section: Cohort Descriptionmentioning

confidence: 99%

“…Further sensitivity analyses were conducted with additional adjustment for BMI, HER2, and tumor-specific CAV1. To accommodate for missing data for these covariates, multiple imputation by chained equations were used and the pooled results were compared to the complete case results as previously performed [13]. Since the CC genotype was more common among TNBC, an additional analysis of rs3815412 in relation to CBCFI was conducted adjusting for TNBC status.…”

Section: Statistical Analysesmentioning

confidence: 99%

“…However, studies have shown that a subset of metachronous contralateral breast cancers represent a metastatic spread of the primary tumor [11,12]. We previously reported that tumor-specific Caveolin-1 (CAV1) was prognostic for both contralateral breast cancer (CAV1 in malignant cells) and locoregional recurrence (CAV1 in stromal cells) [13]. Furthermore, host factors modulated how CAV1 in malignant and stromal cells affected prognosis [13].…”

Section: Introductionmentioning

confidence: 99%

“…We previously reported that tumor-specific Caveolin-1 (CAV1) was prognostic for both contralateral breast cancer (CAV1 in malignant cells) and locoregional recurrence (CAV1 in stromal cells) [13]. Furthermore, host factors modulated how CAV1 in malignant and stromal cells affected prognosis [13]. It would, therefore, be of interest to further elucidate the role of CAV1 in breast cancer by studying CAV1 genotypes.…”

Section: Introductionmentioning

confidence: 99%

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Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer

Godina

Tryggvadottir

Bosch

et al. 2023

Breast Cancer Res Treat

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Purpose Caveolin-1 (CAV1) has been implicated in breast cancer oncogenesis and metastasis and may be a potential prognosticator, especially for non-distant events. CAV1 functions as a master regulator of membrane transport and cell signaling. Several CAV1 SNPs have been linked to multiple cancers, but the prognostic impact of CAV1 SNPs in breast cancer remains unclear. Here, we investigated CAV1 polymorphisms in relation to clinical outcomes in breast cancer. Methods A cohort of 1017 breast cancer patients (inclusion 2002–2012, Sweden) were genotyped using Oncoarray by Ilumina. Patients were followed for up to 15 years. Five out of six CAV1 SNPs (rs10256914, rs959173, rs3807989, rs3815412, and rs8713) passed quality control and were used for haplotype construction. CAV1 genotypes and haplotypes in relation to clinical outcomes were assessed with Cox regression and adjusted for potential confounders (age, tumor characteristics, and adjuvant treatments). Results Only one SNP was associated with lymph node status, no other SNPs or haplotypes were associated with tumor characteristics. The CAV1 rs3815412 CC genotype (5.8% of patients) was associated with increased risk of contralateral breast cancer, adjusted hazard ratio (HRadj) 4.26 (95% CI 1.86–9.73). Moreover, the TTACA haplotype (13% of patients) conferred an increased risk for locoregional recurrence HRadj 2.24 (95% CI 1.24–4.04). No other genotypes or haplotypes were associated with clinical outcome. Conclusion CAV1 polymorphisms were associated with increased risk for locoregional recurrence and contralateral breast cancer. These findings may identify patients that could derive benefit from more tailored treatment to prevent non-distant events, if confirmed.

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Section: Cohort Descriptionmentioning

confidence: 99%

Section: Cohort Descriptionmentioning

confidence: 99%

Section: Statistical Analysesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer

Godina

Tryggvadottir

Bosch

et al. 2023

Breast Cancer Res Treat

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Integrated meta-analyses of genome-wide effects of PM2.5 in human cells identifies widespread dysregulation of genes and pathways associated with cancer progression and patient survival

Bisht,

Dey,

Kulshreshtha

2024

Science of The Total Environment

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Caveolin-1 gene expression provides additional prognostic information combined with PAM50 risk of recurrence (ROR) score in breast cancer

Godina,

Belting,

Vallon-Christersson

et al. 2024

Sci Rep

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

Cited by 5 publications

References 52 publications

Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer

Caveolin-1 genotypes as predictor for locoregional recurrence and contralateral disease in breast cancer

Integrated meta-analyses of genome-wide effects of PM2.5 in human cells identifies widespread dysregulation of genes and pathways associated with cancer progression and patient survival

Caveolin-1 gene expression provides additional prognostic information combined with PAM50 risk of recurrence (ROR) score in breast cancer

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