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  The Proteome of Prostate Cancer Bone Metastasis Reveals Heterogeneity with Prognostic Implications

Iglesias-Gato, D., Thysell, E., Tyanova, S., Crnalic, S., Santos, A., Lima, T. S., et al. (2018). The Proteome of Prostate Cancer Bone Metastasis Reveals Heterogeneity with Prognostic Implications. Clinical Cancer Research, 24(21), 5433-5444. doi:10.1158/1078-0432.CCR-18-1229.

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 Creators:
Iglesias-Gato, Diego1, Author
Thysell, Elin1, Author
Tyanova, Stefka2, Author              
Crnalic, Sead1, Author
Santos, Alberto1, Author
Lima, Thiago S.1, Author
Geiger, Tamar1, Author
Cox, Jürgen2, Author              
Widmark, Anders1, Author
Bergh, Anders1, Author
Mann, Matthias2, Author              
Flores-Morales, Amilcar1, Author
Wikstrom, Pernilla1, Author
Affiliations:
1external, ou_persistent22              
2Mann, Matthias / Proteomics and Signal Transduction, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565159              

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Free keywords: PHASE-III; EXPRESSION; NETWORKS; MEN; QUANTIFICATION; ENZALUTAMIDE; CHEMOTHERAPY; INTEGRATION; PLACEBO; CELLSOncology;
 Abstract: 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.

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Language(s): eng - English
 Dates: 2018
 Publication Status: Published in print
 Pages: 12
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Degree: -

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Title: Clinical Cancer Research
  Other : Clin. Cancer Res.
Source Genre: Journal
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Publ. Info: Denville, NJ : Association for Cancer Research
Pages: - Volume / Issue: 24 (21) Sequence Number: - Start / End Page: 5433 - 5444 Identifier: ISSN: 1078-0432
CoNE: https://pure.mpg.de/cone/journals/resource/954925605818