Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer
Abstract 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...
| Main Authors: | , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2021-02-01
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| Series: | BMC Cancer |
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| Online Access: | https://doi.org/10.1186/s12885-021-07854-0 |
| _version_ | 1818608042273406976 |
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| author | Karoline Berger Sara Rhost Svanheiður Rafnsdóttir Éamon Hughes Ylva Magnusson Maria Ekholm Olle Stål Lisa Rydén Göran Landberg |
| author_facet | Karoline Berger Sara Rhost Svanheiður Rafnsdóttir Éamon Hughes Ylva Magnusson Maria Ekholm Olle Stål Lisa Rydén Göran Landberg |
| author_sort | Karoline Berger |
| collection | DOAJ |
| description | Abstract 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 ERα 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. |
| first_indexed | 2024-12-16T14:36:21Z |
| format | Article |
| id | doaj.art-86319f48f2eb40659a4d1bba84730216 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-12-16T14:36:21Z |
| publishDate | 2021-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-86319f48f2eb40659a4d1bba847302162022-12-21T22:28:05ZengBMCBMC Cancer1471-24072021-02-0121111110.1186/s12885-021-07854-0Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancerKaroline Berger0Sara Rhost1Svanheiður Rafnsdóttir2Éamon Hughes3Ylva Magnusson4Maria Ekholm5Olle Stål6Lisa Rydén7Göran Landberg8Department of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of GothenburgDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of GothenburgDepartment of Oncology, Region Jönköping CountyDepartment of Oncology, Region Jönköping CountyDepartment of Clinical Sciences, Division of Oncology and Pathology, Lund UniversityDepartment of Laboratory Medicine, Institute of Biomedicine, Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of GothenburgAbstract 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 ERα 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.https://doi.org/10.1186/s12885-021-07854-0Breast cancerCancer stem cellsEstrogen receptorProgranulinSortilinTamoxifen |
| spellingShingle | Karoline Berger Sara Rhost Svanheiður Rafnsdóttir Éamon Hughes Ylva Magnusson Maria Ekholm Olle Stål Lisa Rydén Göran Landberg Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer BMC Cancer Breast cancer Cancer stem cells Estrogen receptor Progranulin Sortilin Tamoxifen |
| title | Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer |
| title_full | Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer |
| title_fullStr | Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer |
| title_full_unstemmed | Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer |
| title_short | Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer |
| title_sort | tumor co expression of progranulin and sortilin as a prognostic biomarker in breast cancer |
| topic | Breast cancer Cancer stem cells Estrogen receptor Progranulin Sortilin Tamoxifen |
| url | https://doi.org/10.1186/s12885-021-07854-0 |
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