Proteomics

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


ABSTRACT: Resistance to androgen deprivation therapies leads to metastatic castration-resistant prostate cancer (mCRPC) of adenocarcinoma (AdCa) origin that can transform to emergent aggressive variant prostate cancer (AVPC) which has neuroendocrine (NE)-like features. To this end, we used LuCaP patient-derived xenograft (PDX) tumors, clinically relevant models that reflects and retains 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. When we compared 15 NE versus 33 AdCa PDX samples, we 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 protein and RNA concordance from these tumors revealed increased dissonance in transcriptionally regulated proteins in NE and metabolite interconversion enzymes in AdCa. Keywords: Proteomics, phosphoproteomics, Neuroendocrine, Adenocarcinoma, biomarkers, surfaceome, secretome, blood proteins, prostate cancer, patient-derived xenograft

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Homo Sapiens (ncbitaxon:9606)

SUBMITTER: Justin M. Drake PhD  

PROVIDER: MSV000092139 | MassIVE | Fri Jun 09 14:13:00 BST 2023

SECONDARY ACCESSION(S): PXD042867

REPOSITORIES: MassIVE

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

Sychev Zoi E ZE   Day Abderrahman A   Bergom Hannah E HE   Larson Gabrianne G   Ali Atef A   Ludwig Megan M   Boytim Ella E   Coleman Ilsa I   Corey Eva E   Plymate Stephen R SR   Nelson Peter S PS   Hwang Justin H JH   Drake Justin M JM  

Molecular cancer research : MCR 20240501 5


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 chara  ...[more]

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