Tumor co-expression of progranulin and sortilin as a prognostic biomarker in breast cancer

Autor: Olle Stål, Svanheiður Rafnsdóttir, Éamon Hughes, Göran Landberg, Karoline Berger, Maria Ekholm, Ylva Magnusson, Lisa Rydén, Sara Rhost
Rok vydání: 2020
Předmět:
0301 basic medicine
Oncology
Cancer Research
medicine.medical_treatment
Estrogen receptor
Predictive
Targeted therapy
0302 clinical medicine
Progranulins
Breast cancer
Surgical oncology
Randomized Controlled Trials as Topic
Tissue microarray
Cancer stem cells
Middle Aged
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Prognosis
Progranulin
Sortilin
Tamoxifen
Prognostic
Biomarker
Survival Rate
030220 oncology & carcinogenesis
Lymphatic Metastasis
Neoplastic Stem Cells
Biomarker (medicine)
Female
medicine.drug
Research Article
Adult
medicine.medical_specialty
Antineoplastic Agents
Hormonal
Breast Neoplasms
lcsh:RC254-282
03 medical and health sciences
Cancer stem cell
Internal medicine
mental disorders
Genetics
medicine
Biomarkers
Tumor
Humans
Retrospective Studies
Cancer och onkologi
business.industry
medicine.disease
Adaptor Proteins
Vesicular Transport
030104 developmental biology
Cancer and Oncology
business
Zdroj: BMC Cancer
BMC Cancer, Vol 21, Iss 1, Pp 1-11 (2021)
ISSN: 1471-2407
Popis: 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.
Databáze: OpenAIRE
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