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 |
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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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