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Tumor co-expression...
Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer
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- Berger, Karoline, 1991 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine,Univ Gothenburg, Sweden
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- Rhost, Sara (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine,Univ Gothenburg, Sweden
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- Rafnsdottir, Svanheidur (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine,National University Hospital of Iceland,Univ Gothenburg, Sweden; Natl Univ Hosp Iceland, Iceland
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- Hughes, Éamon (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Centrum för Cancerforskning (SCCR),Department of Laboratory Medicine,Sahlgrenska Center for Cancer Research (SCCR),Univ Gothenburg, Sweden
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- Magnusson, Ylva, 1967 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Sahlgrenska Centrum för Cancerforskning (SCCR),Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Center for Cancer Research (SCCR),Department of Laboratory Medicine,Univ Gothenburg, Sweden
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- Ekholm, Maria (author)
- Linköpings universitet,Linköping University,Lund University,Lunds universitet,Individuell Bröstcancerbehandling,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,Personalized Breast Cancer Treatment,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Jönköping County Council,Institutionen för biomedicinska och kliniska vetenskaper,Medicinska fakulteten,Lund Univ, Sweden; Department of Oncology, Region Jönköping County, Jönköping, Sweden
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- Stål, Olle (author)
- Linköpings universitet,Linköping University,Jönköping County Council,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,3 Department of Oncology, Region Jönköping County, Jönköping, Sweden
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- Rydén, Lisa (author)
- Lund University,Lunds universitet,The Liquid Biopsy och Tumörprogression i Bröstcancer,Forskargrupper vid Lunds universitet,LUCC: Lunds universitets cancercentrum,Övriga starka forskningsmiljöer,The Liquid Biopsy and Tumor Progression in Breast Cancer,Lund University Research Groups,LUCC: Lund University Cancer Centre,Other Strong Research Environments,Lund Univ, Sweden
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- Landberg, Göran, 1963 (author)
- University of Gothenburg,Gothenburg University,Göteborgs universitet,Institutionen för biomedicin, avdelningen för laboratoriemedicin,Sahlgrenska Centrum för Cancerforskning (SCCR),Department of Laboratory Medicine,Sahlgrenska Center for Cancer Research (SCCR),Univ Gothenburg, Sweden
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(creator_code:org_t)
- 2021-02-22
- 2021
- English.
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In: BMC Cancer. - : Springer Science and Business Media LLC. - 1471-2407. ; 21:1
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Abstract
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- Background The growth factor progranulin has been implicated in numerous biological processes such as wound healing, inflammation and progressive tumorigenesis. Both progranulin and its receptor sortilin are known to be highly expressed in subgroups of breast cancer and have been associated with various clinical properties including tamoxifen resistance. Recent data further suggest that progranulin, via its receptor sortilin, drives breast cancer stem cell propagation in vitro and increases metastasis formation in an in vivo breast cancer xenograft model. In this retrospective biomarker analysis, we aimed to determine whether tumor co-expression of progranulin and sortilin has prognostic and treatment predictive values for breast cancer patients. Methods We explored how co-expression of progranulin and sortilin was associated with established clinical markers by analyzing a tissue microarray including 560 randomized premenopausal breast cancer patients receiving either 2 years of tamoxifen treatment or no adjuvant treatment, with a median follow-up time of 28 years. Breast cancer-specific survival was analyzed using Kaplan-Meier and Cox Proportional Hazards regression models to assess the prognostic and predictive value of progranulin and sortilin in relation to known clinical markers. Results Co-expression of progranulin and sortilin was observed in 20% of the breast cancer samples. In untreated patients, prognostic considerations could be detailed separately from treatment prediction and the high progranulin and sortilin expressing subgroup was significantly associated with breast cancer-specific death in multivariable analyses (HR=2.188, CI: 1.317-3.637, p=0.003) along with tumor size, high tumor grade and lymph node positivity. When comparing the untreated patients with tamoxifen treated patients in the ER alpha positive subgroup, co-expression of progranulin and sortilin was not linked to tamoxifen resistance. Conclusion Data suggest that co-expression of progranulin and its receptor sortilin is a novel prognostic biomarker combination identifying a highly malignant subgroup of breast cancer. Importantly, this subpopulation could potentially be targeted with anti-sortilin based therapies.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- Breast cancer
- Cancer stem cells
- Estrogen receptor
- Progranulin
- Sortilin
- Tamoxifen
- Targeted therapy
- Prognostic
- Predictive
- Biomarker
- Oncology
- Breast cancer; Cancer stem cells; Estrogen receptor; Progranulin; Sortilin; Tamoxifen; Targeted therapy; Prognostic; Predictive; Biomarker
Publication and Content Type
- ref (subject category)
- art (subject category)
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BMC Cancer
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- By the author/editor
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Berger, Karoline ...
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Rhost, Sara
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Rafnsdottir, Sva ...
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Hughes, Éamon
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Magnusson, Ylva, ...
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Ekholm, Maria
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Stål, Olle
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Rydén, Lisa
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Landberg, Göran, ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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BMC Cancer
- By the university
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University of Gothenburg
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Lund University
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Linköping University