Paulina Karin Grillo1, Balázs Győrffy2,3,4, Martin Götte5. 1. Department of Gynecology and Obstetrics, Münster University Hospital, Albert-Schweitzer-Campus 1, 11, 48149, Münster, Germany. 2. Department of Bioinformatics, Semmelweis University, Budapest, Hungary. 3. 2nd Department of Pediatrics, Semmelweis University, Budapest, Hungary. 4. TTK Momentum Cancer Biomarker Research Group, Budapest, Hungary. 5. Department of Gynecology and Obstetrics, Münster University Hospital, Albert-Schweitzer-Campus 1, 11, 48149, Münster, Germany. mgotte@uni-muenster.de.
Abstract
PURPOSE: Dysregulated expression of proteoglycans influences the outcome and progression of numerous cancers. Several studies have investigated the role of individual glypicans in cancer, however, the impact of the whole glypican family of heparan sulfate proteoglycans on prognosis of a large patient cohort of breast cancer patients has not yet been investigated. In the present study, our aim was to investigate the prognostic power of the glypicans in breast cancer patients. METHODS: We used a public database including both gene expression data and survival information for 3951 breast cancer patients to determine the prognostic value of glypicans on relapse-free survival using Cox regression analysis. Moreover, we performed quantitative Real-Time PCR to determine glypican gene expression levels in seven representative breast cancer cell lines. RESULTS: We found that high GPC3 levels were associated with a better prognosis in overall breast cancer patients. When stratified by hormone receptor status, we found that in worse prognosis subtypes low GPC1 levels correlate with a longer relapse-free survival, and in more favorable subtypes low GPC6 was associated with longer survival. CONCLUSION: Our study concludes that glypicans could act as subtype-specific biomarkers for the prognosis of breast cancer patients and sparks hope for future research on glypicans possibly eventually providing targets for the treatment of the disease.
PURPOSE: Dysregulated expression of proteoglycans influences the outcome and progression of numerous cancers. Several studies have investigated the role of individual glypicans in cancer, however, the impact of the whole glypican family of heparan sulfate proteoglycans on prognosis of a large patient cohort of breast cancerpatients has not yet been investigated. In the present study, our aim was to investigate the prognostic power of the glypicans in breast cancerpatients. METHODS: We used a public database including both gene expression data and survival information for 3951 breast cancerpatients to determine the prognostic value of glypicans on relapse-free survival using Cox regression analysis. Moreover, we performed quantitative Real-Time PCR to determine glypican gene expression levels in seven representative breast cancer cell lines. RESULTS: We found that high GPC3 levels were associated with a better prognosis in overall breast cancerpatients. When stratified by hormone receptor status, we found that in worse prognosis subtypes low GPC1 levels correlate with a longer relapse-free survival, and in more favorable subtypes low GPC6 was associated with longer survival. CONCLUSION: Our study concludes that glypicans could act as subtype-specific biomarkers for the prognosis of breast cancerpatients and sparks hope for future research on glypicans possibly eventually providing targets for the treatment of the disease.
Entities:
Keywords:
Breast cancer; Gene expression; Glypicans; Prognosis; Proteoglycans; Survival analysis
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