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PXD008918

PXD008918 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleProteomics analysis of monocyte-derived hepatocyte-like cells identifies integrin beta 3 as a specific biomarker for drug-induced liver injury by diclofenac
DescriptionIdiosyncratic 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.
HostingRepositoryPRIDE
AnnounceDate2024-10-22
AnnouncementXMLSubmission_2024-10-22_04:43:01.747.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterGarwin Pichler
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02018-02-09 07:27:47ID requested
12018-07-23 08:51:46announced
22024-10-22 04:43:02announced2024-10-22: Updated project metadata.
Publication List
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;
Keyword List
curator keyword: Biomedical
submitter keyword: DILI, Monocyte.derived hepatocyte-like cells, Drug-development, Proteomics, biomarker
Contact List
Andreas Benesic
contact affiliationMetaheps GmbH, Germany Department of Medicine 2, Liver Centre Munich®, University Hospital Munich (KUM) Campus Grosshadern, Munich, Germany, Germany
contact emailAndreas.Benesic@med.uni-muenchen.de
lab head
Garwin Pichler
contact affiliationPreOmics
contact emailpichler@preomics.com
dataset submitter
Full Dataset Link List
Dataset FTP location
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PRIDE project URI
Repository Record List
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