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

Autor:	Sychev ZE; Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota., Day A; Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota.; Institute for Health Informatics, University of Minnesota, Minneapolis, Minnesota., Bergom HE; Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota., Larson G; Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota., Ali A; Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota., Ludwig M; Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota., Boytim E; Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota., Coleman I; Fred Hutchinson Cancer Center, Seattle, Washington., Corey E; Department of Urology, University of Washington, Seattle, Washington., Plymate SR; Department of Urology, University of Washington, Seattle, Washington.; Division of Gerontology and Geriatrics Medicine, University of Washington, Seattle, Washington.; Geriatric Research Education and Clinical Center, Seattle Veterans Affairs Medical Center, Seattle Washington., Nelson PS; Fred Hutchinson Cancer Center, Seattle, Washington., Hwang JH; Division of Hematology, Oncology and Transplantation, University of Minnesota, Minneapolis, Minnesota.; Department of Medicine, University of Minnesota Masonic Cancer Center, Minneapolis, Minnesota.; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota., Drake JM; Department of Pharmacology, University of Minnesota, Minneapolis, Minnesota.; Masonic Cancer Center, University of Minnesota, Minneapolis, Minnesota.; Department of Urology, University of Minnesota, Minneapolis, Minnesota.
Jazyk:	angličtina
Zdroj:	Molecular cancer research : MCR [Mol Cancer Res] 2024 May 02; Vol. 22 (5), pp. 452-464.
DOI:	10.1158/1541-7786.MCR-23-0976
Abstrakt:	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. (©2024 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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