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Cited by 13Prostate Cancer Treatment and ResearchAdvanced Proteomics Techniques and ApplicationsProstate Cancer Diagnosis and Treatment

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Unraveling the Global Proteome and Phosphoproteome of Prostate Cancer Patient-Derived Xenografts

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Sychev, Zoi E., Day, Abderrahman, Bergom, Hannah E., Larson, Gabrianne, Ali, Atef, Ludwig, Megan, Boytim, Ella, Coleman, Ilsa, Corey, Eva, Plymate, Stephen R., Nelson, Peter S., Hwang, Justin H., Drake, Justin M.·2024·Molecular Cancer Research
DOI 10.1158/1541-7786.mcr-23-0976PMC PMC11063764

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Abstract

Resistance to androgen-deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform into emergent aggressive variant prostate cancer (AVPC), which has neuroendocrine (NE)-like features. In this work, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflect and retain key features of the tumor from advanced prostate cancer patients. Here we performed proteome and phosphoproteome characterization of 48 LuCaP PDX tumors and identified over 94,000 peptides and 9,700 phosphopeptides corresponding to 7,738 proteins. We compared 15 NE versus 33 AdCa samples, which included six different PDX tumors for each group in biological replicates, and identified 309 unique proteins and 476 unique phosphopeptides that were significantly altered and corresponded to proteins that are known to distinguish these two phenotypes. Assessment of concordance from PDX tumor-matched protein and mRNA revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa. Implications: Overall, our study highlights the importance of protein-based identification when compared with RNA and provides a rich resource of new and feasible targets for clinical assay development and in understanding the underlying biology of these tumors.

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Metadata

Authors
Sychev, Z. E., Day, A., Bergom, H. E., Larson, G., Ali, A., Ludwig, M., Boytim, E., Coleman, I., Corey, E., Plymate, S. R., Nelson, P. S., Hwang, J. H., & Drake, J. M.
Affiliations
  • University of Minnesota (US)
  • Fred Hutch Cancer Center (US)
  • University of Washington (US)
  • United States Department of Veterans Affairs (US)
Corresponding author
Drake, Justin M.
ORCID
Venue
Molecular Cancer Research
Publisher
American Association for Cancer Research (AACR)
Published
2024-02-12
Volume
22
Issue
5
Pages
452-464
ISSN
  • 1541-7786 (ISSN-L)
  • 1557-3125
DOI
10.1158/1541-7786.mcr-23-0976
PMC
PMC11063764
OpenAlex
W4391755053
Cited by
13
References
2
Citations by year
2026: 3 · 2025: 4 · 2024: 6
FWCI
4.33
Type
journal article
Language
en
Open access
Licence
Locations
  • Molecular Cancer Research (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • PubMed Central (submittedVersion, cc-by-nc-nd)
Funders
  • U.S. Department of Defense (E01 W81XWH-20-1-0070-P00002, W81XWH-18-1-0542)
  • National Institutes of Health (P50 CA97186, CA163227, R01CA269801)
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
castration-resistant prostate cancer, neuroendocrine prostate cancer, adenocarcinoma, patient-derived xenografts, proteome, phosphoproteome, androgen deprivation therapy resistance

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