Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
MetadataShow full item record
CitationBerger K, Rhost S, Rafnsdóttir S, Hughes É, Magnusson Y, Ekholm M, Stål O, Rydén L, Landberg G. Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer. BMC Cancer. 2021 Feb 22;21(1):185. doi: 10.1186/s12885-021-07854-0.
AbstractBackground: 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. Keywords: Biomarker; Breast cancer; Cancer stem cells; Estrogen receptor; Predictive; Prognostic; Progranulin; Sortilin; Tamoxifen; Targeted therapy.
DescriptionTo access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download
- Sortilin inhibition limits secretion-induced progranulin-dependent breast cancer progression and cancer stem cell expansion.
- Authors: Rhost S, Hughes É, Harrison H, Rafnsdottir S, Jacobsson H, Gregersson P, Magnusson Y, Fitzpatrick P, Andersson D, Berger K, Ståhlberg A, Landberg G
- Issue date: 2018 Nov 20
- Co-expression of estrogen receptor alpha and Apolipoprotein D in node positive operable breast cancer--possible relevance for survival and effects of adjuvant tamoxifen in postmenopausal patients.
- Authors: Søiland H, Skaland I, Varhaug JE, Kørner H, Janssen EA, Gudlaugsson E, Baak JP, Søreide JA
- Issue date: 2009
- Prognostic and predictive value of androgen receptor expression in postmenopausal women with estrogen receptor-positive breast cancer: results from the Breast International Group Trial 1-98.
- Authors: Kensler KH, Regan MM, Heng YJ, Baker GM, Pyle ME, Schnitt SJ, Hazra A, Kammler R, Thürlimann B, Colleoni M, Viale G, Brown M, Tamimi RM
- Issue date: 2019 Feb 22
- Hypoxia inducible factor-1alpha is a prognostic marker in premenopausal patients with intermediate to highly differentiated breast cancer but not a predictive marker for tamoxifen response.
- Authors: Kronblad A, Jirström K, Rydén L, Nordenskjöld B, Landberg G
- Issue date: 2006 May 15
- Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial.
- Authors: Albain KS, Barlow WE, Shak S, Hortobagyi GN, Livingston RB, Yeh IT, Ravdin P, Bugarini R, Baehner FL, Davidson NE, Sledge GW, Winer EP, Hudis C, Ingle JN, Perez EA, Pritchard KI, Shepherd L, Gralow JR, Yoshizawa C, Allred DC, Osborne CK, Hayes DF, Breast Cancer Intergroup of North America.
- Issue date: 2010 Jan