Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer
Berger, Karoline ; Rhost, Sara ; Rafnsdóttir, Svanheiður ; Hughes, Éamon ; Magnusson, Ylva ; Ekholm, Maria LU ; Stål, Olle ; Rydén, Lisa LU
and Landberg, Göran
LU
(2021)
In BMC Cancer
21(1).
- 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... (More)
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.
(Less)
- author
- Berger, Karoline
; Rhost, Sara
; Rafnsdóttir, Svanheiður
; Hughes, Éamon
; Magnusson, Ylva
; Ekholm, Maria
LU
; Stål, Olle
; Rydén, Lisa
LU
and Landberg, Göran
LU
- organization
- publishing date
- 2021
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Biomarker, Breast cancer, Cancer stem cells, Estrogen receptor, Predictive, Prognostic, Progranulin, Sortilin, Tamoxifen, Targeted therapy
- in
- BMC Cancer
- volume
- 21
- issue
- 1
- article number
- 185
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85101405429
- pmid:33618683
- ISSN
- 1471-2407
- DOI
- 10.1186/s12885-021-07854-0
- language
- English
- LU publication?
- yes
- id
- 20785a6b-9c83-4b11-91cc-b85addfcc671
- date added to LUP
- 2021-03-08 09:02:00
- date last changed
- 2024-06-14 10:51:40
@article{20785a6b-9c83-4b11-91cc-b85addfcc671,
abstract = {{<p>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.</p>}},
author = {{Berger, Karoline and Rhost, Sara and Rafnsdóttir, Svanheiður and Hughes, Éamon and Magnusson, Ylva and Ekholm, Maria and Stål, Olle and Rydén, Lisa and Landberg, Göran}},
issn = {{1471-2407}},
keywords = {{Biomarker; Breast cancer; Cancer stem cells; Estrogen receptor; Predictive; Prognostic; Progranulin; Sortilin; Tamoxifen; Targeted therapy}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{BMC Cancer}},
title = {{Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer}},
url = {{http://dx.doi.org/10.1186/s12885-021-07854-0}},
doi = {{10.1186/s12885-021-07854-0}},
volume = {{21}},
year = {{2021}},
}