PXD007657

PXD007657 is an original dataset announced via ProteomeXchange.

Title	Multi-omics biomarker pipeline reveals elevated levels of protein-glutamine gamma-glutamyltransferase 4 in seminal plasma of prostate cancer patients
Description	Prostate-specific antigen, a blood serum biomarker of prostate cancer, lacks specificity and prognostic significance, so considerable efforts are devoted to developing novel biomarkers. Seminal plasma, due to its proximity to prostate, is a promising fluid for biomarker discovery and non-invasive diagnostics. In this study, we investigated if seminal plasma proteins could increase specificity of detecting primary prostate cancer and discriminate between high- and low-grade cancers. To select 148 most promising biomarker candidates, we combined proteins identified through five independent data mining or experimental approaches: tissue transcriptomics, seminal plasma proteomics, cell secretomics, tissue specificity and androgen regulation. A rigorous biomarker development pipeline based on targeted proteomics assays was designed to evaluate the most promising candidates. We qualified 77 and verified 19 proteins in seminal plasma of 67 negative biopsy and 155 prostate cancer patients. Verification revealed a prostate-specific, secreted and androgen-regulated protein-glutamine gamma-glutamyltransferase 4 (TGM4), which could predict prostate cancer on biopsy and outperformed age and serum PSA. Machine-learning approaches also revealed improved multi-marker combinations for diagnosis and prognosis. In the independent verification set measured by an in-house ELISA, TGM4 was up-regulated 3.7-fold (P=0.006) and revealed AUC 0.66 for detecting prostate cancer on biopsy for patients serum PSA≥4 ng/mL and age≥50. Low levels of TGM4 (120 pg/mL) were detected in blood serum, but could not differentiate between negative biopsy, prostate cancer or prostate inflammation. To conclude, performance of TGM4 warrants its further investigation within the distinct genomic subtypes of prostate cancer and evaluation for the inclusion into emerging multi-biomarker panels.
HostingRepository	PRIDE
AnnounceDate	2019-08-02
AnnouncementXML	Submission_2019-08-02_02:41:30.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Andrei Drabovich
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; acetylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2017-09-05 02:27:59	ID requested
⏵ 1	2019-08-02 02:41:31	announced

Drabovich AP, Saraon P, Drabovich M, Karakosta TD, Dimitromanolakis A, Hyndman ME, Jarvi K, Diamandis EP, Multi-omics Biomarker Pipeline Reveals Elevated Levels of Protein-glutamine Gamma-glutamyltransferase 4 in Seminal Plasma of Prostate Cancer Patients. Mol Cell Proteomics, 18(9):1807-1823(2019) [pubmed]

curator keyword: Biomedical

submitter keyword: prostate cancer

biomarker discovery

seminal plasma

proteomics

mass spectrometry

selected reaction monitoring

TGM4

protein-glutamine gamma-glutamyltransferase 4

Andrei P. Drabovich
contact affiliation	Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada Clinical Biochemistry, University Health Network, Toronto
contact email	andrei.drabovich@utoronto.ca
lab head
Andrei Drabovich
contact affiliation	University of Toronto
contact email	andrei.drabovich@utoronto.ca
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD007657
     1. Label: PRIDE project
     2. Name: Multi-omics biomarker pipeline reveals elevated levels of protein-glutamine gamma-glutamyltransferase 4 in seminal plasma of prostate cancer patients