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The Proteome of Prostate Cancer Bone Metastasis Reveals Heterogeneity with Prognostic Implications
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Pathology.
Umeå University, Faculty of Medicine, Department of Surgical and Perioperative Sciences, Orthopaedics.
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2018 (English)In: Clinical Cancer Research, ISSN 1078-0432, E-ISSN 1557-3265, Vol. 24, no 21, p. 5433-5444Article in journal (Refereed) Published
Abstract [en]

Purpose: Bone is the most predominant site of distant metastasis in prostate cancer, and patients have limited therapeutic options at this stage.

Experimental Design: We performed a system-wide quantitative proteomic analysis of bone metastatic prostate tumors from 22 patients operated to relieve spinal cord compression. At the time of surgery, most patients had relapsed after androgen-deprivation therapy, while 5 were previously untreated. An extended cohort of prostate cancer bone metastases (n = 65) was used for immunohistochemical validation.

Results: On average, 5,067 proteins were identified and quantified per tumor. Compared with primary tumors (n = 26), bone metastases were more heterogeneous and showed increased levels of proteins involved in cell-cycle progression, DNA damage response, RNA processing, and fatty acid b-oxidation; and reduced levels of proteins were related to cell adhesion and carbohydrate metabolism. Within bone metastases, we identified two phenotypic subgroups: BM1, expressing higher levels of AR canonical targets, and mitochondrial and Golgi apparatus resident proteins; and BM2, with increased expression of proliferation and DNA repair-related proteins. The two subgroups, validated by the inverse correlation between MCM3 and prostate specific antigen immunoreactivity, were related to disease prognosis, suggesting that this molecular heterogeneity should be considered when developing personalized therapies.

Conclusions: This work is the first system-wide quantitative characterization of the proteome of prostate cancer bone metastases and a valuable resource for understanding the etiology of prostate cancer progression. (C) 2018 AACR.

Place, publisher, year, edition, pages
American Association for Cancer Research , 2018. Vol. 24, no 21, p. 5433-5444
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:umu:diva-153547DOI: 10.1158/1078-0432.CCR-18-1229ISI: 000448895100025PubMedID: 30042207OAI: oai:DiVA.org:umu-153547DiVA, id: diva2:1265270
Funder
Swedish Research Council, K2013-64X-20407-04-3Swedish Cancer Society, CAN 2015/732Swedish Cancer Society, CAN 2016/824Swedish Cancer Society, CAN 2013/1324Swedish Cancer Society, 130293Swedish Foundation for Strategic Research , RB13-0119Novo Nordisk, NNF14CC0001Available from: 2018-11-22 Created: 2018-11-22 Last updated: 2018-11-22Bibliographically approved

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Thysell, ElinCrnalic, SeadWidmark, AndersWikström, Pernilla

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