PXD019945

PXD019945 is an original dataset announced via ProteomeXchange.

Title	Identification of candidate circulating glucocorticoid response biomarkers in humans using a proteomic approach
Description	Glucocorticoids used in pharmacological doses for the treatment of a variety of medical conditions, and endogenous glucocorticoid excess – Cushing’s syndrome, may result in several adverse effects, but currently there is no clinically useful biomarker of glucocorticoid activity. A three-phase protein biomarker discovery strategy was used. Proteomic biomarker discovery and qualification was conducted on the secretome of ex vivo-stimulated peripheral blood mononuclear cells (PBMC) isolated from 6 volunteers, incubated ± dexamethasone 100 ng/mL for 4h and 24h. Untargeted proteomics with label-free quantification (LFQ) was conducted to discover candidate proteins which were quantified using targeted proteomics by a custom multiple reaction monitoring mass spectrometry (MRM-MS) assay. Five proteins were selected for serum measurement by immunoassay in 20 healthy volunteers, with blood drawn at baseline and 12h after 4 mg oral dexamethasone. Paired analysis of the discovery proteomics data (576 and 280 proteins for the 4h and 24h secretomes, respectively) generated a shortlist of candidates which were qualified using MRM-MS to obtain protein level intensity data for 39 proteins. In the validation cohort, 3/5 proteins were dexamethasone-responsive, two significantly decreased: lysozyme C (mean±SEM) – 101±5.5 vs 67±4.4 ng/mL, (P<0.0001); nucleophosmin-1 (median (interquartile range)) – 16.6 (14.4-18.4) vs 14.2 (11.1-17.4) ng/mL, (P<0.01), while high mobility group box 2 (mean±SEM) significantly increased – 819±34 vs 984±60 pg/mL (P<0.01). Using an ex vivo proteomic approach in PBMC, we have identified and verified circulating glucocorticoid-responsive proteins which may have potential as serum biomarkers.
HostingRepository	PRIDE
AnnounceDate	2021-03-15
AnnouncementXML	Submission_2021-03-14_23:15:45.758.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Thomas Stoll
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive Plus

Revision	Datetime	Status	ChangeLog Entry
0	2020-06-22 03:10:17	ID requested
1	2021-03-14 16:16:30	announced
⏵ 2	2021-03-14 23:15:46	announced	2021-03-15: Updated project metadata.

Inder WJ, Mohamed A, Keshvari S, Barclay JL, Ruelcke JE, Stoll T, Nolan BJ, Cesana-Nigro N, Hill MM, Ex vivo glucocorticoid-induced secreted proteome approach for discovery of glucocorticoid-responsive proteins in human serum. Proteomics Clin Appl, 15(2-3):e2000078(2021) [pubmed]

10.1002/PRCA.202000078;

submitter keyword: Proteomics, PBMC, glucocorticoid, dexamethasone, biomarker

Michelle M. Hill
contact affiliation	QIMR Berghofer Medical Research Institute, Brisbane QLD 4006, Australia
contact email	Michelle.Hill@qimrberghofer.edu.au
lab head
Thomas Stoll
contact affiliation	QIMR Berghofer Medical Research Institute 300 Herston Road, Herston QLD 4006
contact email	thomas.stoll@qimrberghofer.edu.au
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2021/03/PXD019945

PRIDE project URI

• PRIDE
  1. PXD019945
     1. Label: PRIDE project
     2. Name: Identification of candidate circulating glucocorticoid response biomarkers in humans using a proteomic approach