PXD008918 is an
original dataset announced via ProteomeXchange.
Dataset Summary
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 |
Dataset History
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. |
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 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 | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD008918
- Label: PRIDE project
- Name: Proteomics analysis of monocyte-derived hepatocyte-like cells identifies integrin beta 3 as a specific biomarker for drug-induced liver injury by diclofenac