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Multi-omics Biomarker Pipeline Reveals Elevated Levels of Protein-glutamine Gamma-glutamyltransferase 4 in Seminal Plasma of Prostate Cancer Patients.
Drabovich, Andrei P; Saraon, Punit; Drabovich, Mikalai; Karakosta, Theano D; Dimitromanolakis, Apostolos; Hyndman, M Eric; Jarvi, Keith; Diamandis, Eleftherios P.
Afiliación
  • Drabovich AP; ‡Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5T 3L9 Canada; §Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, M5T 3L9 Canada; ¶Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M
  • Saraon P; ‡Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5T 3L9 Canada.
  • Drabovich M; ‖Independent researcher, Palo Alto, California 94303.
  • Karakosta TD; §Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, M5T 3L9 Canada.
  • Dimitromanolakis A; §Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, M5T 3L9 Canada.
  • Hyndman ME; **Department of Surgery, Division of Urology, Southern Alberta Institute of Urology, University of Calgary, Calgary, AB T2V 1P9, Canada.
  • Jarvi K; ‡‡Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, Toronto, Ontario, M5T 3L9 Canada; §§Department of Surgery, Division of Urology, Mount Sinai Hospital, University of Toronto, Toronto, Ontario, M5T 3L9 Canada. Electronic address: keith.jarvi@sinaihealthsystem.ca.
  • Diamandis EP; ‡Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario, M5T 3L9 Canada; §Department of Clinical Biochemistry, University Health Network, Toronto, Ontario, M5T 3L9 Canada; ¶Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, Ontario, M
Mol Cell Proteomics ; 18(9): 1807-1823, 2019 09.
Article en En | MEDLINE | ID: mdl-31249104
ABSTRACT
Seminal plasma, because of its proximity to prostate, is a promising fluid for biomarker discovery and noninvasive diagnostics. In this study, we investigated if seminal plasma proteins could increase diagnostic specificity of detecting primary prostate cancer and discriminate between high- and low-grade cancers. To select 147 most promising biomarker candidates, we combined proteins identified through five independent experimental or data mining approaches tissue transcriptomics, seminal plasma proteomics, cell line secretomics, tissue specificity, and androgen regulation. A rigorous biomarker development pipeline based on selected reaction monitoring assays was designed to evaluate the most promising candidates. As a result, we qualified 76, and verified 19 proteins in seminal plasma of 67 negative biopsy and 152 prostate cancer patients. Verification revealed a prostate-specific, secreted and androgen-regulated protein-glutamine gamma-glutamyltransferase 4 (TGM4), which predicted prostate cancer on biopsy and outperformed age and serum Prostate-Specific Antigen (PSA). A machine-learning approach for data analysis provided improved multi-marker combinations for diagnosis and prognosis. In the independent verification set measured by an in-house immunoassay, TGM4 protein was upregulated 3.7-fold (p = 0.006) and revealed AUC = 0.66 for detecting prostate cancer on biopsy for patients with serum PSA ≥4 ng/ml and age ≥50. Very low levels of TGM4 (120 pg/ml) were detected in blood serum. Collectively, our study demonstrated rigorous evaluation of one of the remaining and not well-explored prostate-specific proteins within the medium-abundance proteome of seminal plasma. Performance of TGM4 warrants its further investigation within the distinct genomic subtypes and evaluation for the inclusion into emerging multi-biomarker panels.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Semen / Biomarcadores de Tumor / Transglutaminasas Límite: Adult / Aged / Humans / Male / Middle aged Idioma: En Revista: Mol Cell Proteomics Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2019 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Semen / Biomarcadores de Tumor / Transglutaminasas Límite: Adult / Aged / Humans / Male / Middle aged Idioma: En Revista: Mol Cell Proteomics Asunto de la revista: BIOLOGIA MOLECULAR / BIOQUIMICA Año: 2019 Tipo del documento: Article
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