PXD008918

PXD008918 is an original dataset announced via ProteomeXchange.

Title	Proteomics analysis of monocyte-derived hepatocyte-like cells identifies integrin beta 3 as a specific biomarker for drug-induced liver injury by diclofenac
Description	Idiosyncratic drug-induced liver injury (iDILI) is a major cause of acute liver failure resulting in liver transplantation or death. Prediction and diagnosis of iDILI remain a great challenge, as current models provide unsatisfying results in terms of sensitivity, specificity and prognostic value. The absence of appropriate tools for iDILI detection also impairs the development of reliable biomarkers. Here, we report on a new method for identification of drug-specific biomarkers. We combined the advantages of monocyte-derived hepatocyte-like (MH) cells, able to mimic individual characteristics, with those of a novel mass spectrometry (MS)-based proteomics technology to assess potential biomarkers for Diclofenac-induced DILI. We found over 2700 proteins differentially regulated in MH cells derived from individual patients. Herefrom, we identified integrin beta 3 (ITGB3) to be specifically upregulated in Diclofenac-treated MH cells from Diclofenac-DILI patients compared to control groups. Finally, we validated ITGB3 by flow cytometry analysis of whole blood and histological staining of liver biopsies derived from patients diagnosed with Diclofenac-DILI. In summary, our results show that biomarker candidates can be identified by proteomics analysis of MH cells. Application of this method to a broader range of drugs in the future will exploit its full potential for the development of drug-specific biomarkers.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:43:01.747.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Garwin Pichler
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2018-02-09 07:27:47	ID requested
1	2018-07-23 08:51:46	announced
⏵ 2	2024-10-22 04:43:02	announced	2024-10-22: Updated project metadata.

Dragoi D, Benesic A, Pichler G, Kulak NA, Bartsch HS, Gerbes AL, Proteomics Analysis of Monocyte-Derived Hepatocyte-Like Cells Identifies Integrin Beta 3 as a Specific Biomarker for Drug-Induced Liver Injury by Diclofenac. Front Pharmacol, 9():699(2018) [pubmed]

10.3389/fphar.2018.00699;

curator keyword: Biomedical

submitter keyword: DILI, Monocyte.derived hepatocyte-like cells, Drug-development, Proteomics, biomarker

Andreas Benesic
contact affiliation	Metaheps GmbH, Germany Department of Medicine 2, Liver Centre Munich®, University Hospital Munich (KUM) Campus Grosshadern, Munich, Germany, Germany
contact email	Andreas.Benesic@med.uni-muenchen.de
lab head
Garwin Pichler
contact affiliation	PreOmics
contact email	pichler@preomics.com
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/2018/07/PXD008918

PRIDE project URI

• PRIDE
  1. PXD008918
     1. Label: PRIDE project
     2. Name: Proteomics analysis of monocyte-derived hepatocyte-like cells identifies integrin beta 3 as a specific biomarker for drug-induced liver injury by diclofenac