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- Godina, Christopher, et al.
(författare)
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High Caveolin-1 mRNA expression in triple-negative breast cancer is associated with an aggressive tumor microenvironment, chemoresistance, and poor clinical outcome
- 2024
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 19:7, s. 1-21
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Tidskriftsartikel (refereegranskat)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 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.
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- Godina, Christopher, et al.
(författare)
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Interplay between Caveolin-1 and body and tumor size affects clinical outcomes in breast cancer
- 2022
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Ingår i: Translational Oncology. - : Elsevier. - 1944-7124 .- 1936-5233. ; 22
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Tidskriftsartikel (refereegranskat)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. 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, epithelialmesenchymal 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/m(2) (P-interaction = 0.002), waist > 80 cm (P-interaction = 0.005), and invasive tumor size (pT2/3/4) (P-interaction = 0.028). In low-risk patients only, strong stromal CAV1 significantly increased recurrence risk (HRs(adj) > 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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- Larsson, Anna H, et al.
(författare)
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Overexpression of podocalyxin-like protein is an independent factor of poor prognosis in colorectal cancer
- 2011
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 105:5, s. 666-672
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Podocalyxin-like 1 (PODXL) is a cell-adhesion glycoprotein and stem cell marker that has been associated with an aggressive tumour phenotype and poor prognosis in several forms of cancer. In this study, we investigated the prognostic impact of PODXL expression in colorectal cancer (CRC). METHODS: Using tissue microarrays and immunohistochemistry, PODXL expression was evaluated in 536 incident CRC cases from a prospective, population-based cohort study. Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the impact of PODXL expression on cancer-specific survival (CSS) and overall survival (OS). RESULTS: High PODXL expression was significantly associated with unfavourable clinicopathological characteristics, a shorter CSS (hazard ratio (HR) = 1.98; 95% confidence interval (CI) 1.38-2.84, P < 0.001) and 5-year OS (HR = 1.85; 95% CI 1.29-2.64, P = 0.001); the latter remaining significant in multivariate analysis (HR = 1.52; 95% CI 1.03-2.25, P = 0.036). In addition, in curatively resected stage III (T1-4, N1-2, M0) patients (n = 122) with tumours with high PODXL expression, a significant benefit from adjuvant chemotherapy was demonstrated (p(interaction) = 0.004 for CSS and 0.015 for 5-year OS in multivariate analysis). CONCLUSION: Podocalyxin-like 1 expression is an independent factor of poor prognosis in CRC. Our results also suggest that PODXL may be a useful marker to stratify patients for adjuvant chemotherapy.
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- Svensson, Katrin, et al.
(författare)
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Chondroitin sulfate expression predicts poor outcome in breast cancer.
- 2011
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Ingår i: International Journal of Oncology. - : Spandidos Publications. - 1019-6439 .- 1791-2423. ; 39, s. 1421-1428
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Tidskriftsartikel (refereegranskat)abstract
- Experimental studies have established that the sulfated glycosaminoglycans heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and growth factors that drive the malignant cell phenotype and the remodelling of the surrounding tumor stroma. However, the clinical relevance of these studies remains ill-defined. The present study investigates the significance of chondroitin sulfate expression in malignant cells and the stroma, respectively, of tumors from two independent cohorts of breast cancer patients (cohort I: 144 patients, 130 evaluable samples; cohort II: 498 patients, 469 evaluable samples; ER-positive patients ~86% in both cohorts). Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the relationship between chondroitin sulfate and recurrence-free and overall survival. High chondroitin sulfate expression in malignant cells was shown to predict shorter recurrence-free survival (P=0.007, cohort I; P=0.024, cohort II) and overall survival (cohort I: P=0.044; cohort II: P<0.001) in both cohorts. In multivariate analysis, high chondroitin sulfate in malignant cells was shown to be an independent, predictive factor of poor overall survival (cohort I: hazard ratio 2.28: 95% confidence interval 1.08-4.81, P=0.031; cohort II: hazard ratio 1.71: 95% confidence interval 1.23-2.38, P=0.001). However, chondroitin sulfate in the stroma showed no correlation with known markers of tumor aggressiveness or with clinical outcome in either cohort. Our data suggest that high chondroitin sulfate expression in malignant cells is associated with an adverse outcome in patients with primary breast cancer, supporting the idea of a functional and potentially targetable role of chondroitin sulfate in tumor disease.
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