The DOI matches its Crossref record; 7 of the 7 references it cites were found in a registry or an index.
The Proteome of Prostate Cancer Bone Metastasis Reveals Heterogeneity with Prognostic Implications
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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 β-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. Clin Cancer Res; 24(21); 5433–44. ©2018 AACR.
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Metadata
- Authors
- Iglesias-Gato, D., Thysell, E., Tyanova, S., Crnalic, S., Santos, A., Lima, T. S., Geiger, T., Cox, J., Widmark, A., Bergh, A., Mann, M., Flores-Morales, A., & Wikström, P.
- Affiliations
- 1Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
- Umeå University (SE)
- Max Planck Institute of Biochemistry (DE)
- University of Copenhagen (DK)
- Tel Aviv University (IL)
- ORCID
- Venue
- Clinical Cancer Research
- Published
- 2018-11-01
- Volume
- 24
- Issue
- 21
- Pages
- 5433-5444
- ISSN
- 1078-0432 (ISSN-L)
- 1557-3265
- OpenAlex
- W2883308042
- Cited by
- 106
- References
- 7
- Citations by year
- 2026: 12 · 2025: 7 · 2024: 18 · 2023: 8 · 2022: 12 · 2021: 18 · 2020: 18 · 2019: 12 · 2018: 1
- FWCI
- 9.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Clinical Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Funders
- Danish Research Council (DFF 4004-00450)
- Danish Cancer Society (R90-A6060-14-S2)
- Swedish Research Council (K2013-64X-20407-04-3)
- Swedish Cancer Society (CAN 2016/824, CAN 2013/1324, CAN 2015/732)
- Swedish Foundation for Strategic Research (RB13-0119)
- Novo Nordisk Foundation (NNF14CC0001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Prostate Cancer Treatment and Research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Urology › Prostate Cancer Diagnosis and Treatment
- Keywords
- prostate cancer, bone metastasis, tumor proteome, proteomic heterogeneity, prognostic factors, androgen receptor, MCM3, prostate-specific antigen, DNA repair, cell cycle, DNA damage response, fatty acid beta-oxidation, cell adhesion, mitochondrial proteins, phenotypic subgroups, spinal cord compression, androgen deprivation therapy
- MeSH terms
- Aged, Biopsy, Bone Neoplasms, Combined Modality Therapy, Humans, Male, Middle Aged, Models, Biological, Prognosis, Prostatic Neoplasms, Biomarkers, Tumor, Computational Biology, Proteome, Gene Expression Profiling, Proteomics, Transcriptome, Neoplasm Grading
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