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PXD072667-1

PXD072667 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleToxicoproteomics of HepG2 Reveals Translational Biomarkers of Paracetamol-Induced Liver Injury and Recovery
DescriptionDrug-induced liver injury (DILI) is a leading cause of acute liver failure (ALF) and a major obstacle in drug development, reflecting the limited predictive value of animal models and lack of robust,mechanism-based biomarkers. Human in vitro systems, coupled with unbiased omics approaches, have emerged as a potential alternative strategy. Here, quantitative toxicoproteomics was applied to paracetamol (acetaminophen; APAP)-exposed HepG2 cells to identify translational biomarkers of APAP-induced DILI. Cells were exposed to the IC₅₀ concentration of APAP for 8 h (injury phase), followed by drug withdrawal and a 24 h recovery phase. LC–MS/MS analysis quantified 1,478 proteins and revealed increased protein secretion upon APAP exposure. Notably, comparison of the proteomic dataset against available enriched proteomic profiles of ALF patients’ serum confirmed the clinical relevance of the molecular signature obtained. Injury-phase upregulated proteins, including KRT18 and HMGB1, recapitulated known clinical DILI biomarkers. Conversely, recovery was characterized by enrichment of the liver regeneration markers AFP, APOA1 and HP, enabling discrimination between injury and regeneration. HPD, S100A6 and TXNRD1 emerged as candidate diagnostic biomarkers, while SERPINA1 and complement components (C3, C5) showed prognostic potential. Collectively, this study demonstrates that toxicoproteomics applied to human in vitro hepatic models, validated against patient-derived data, enables the discovery of novel translational biomarkers of liver injury and recovery.
HostingRepositoryPRIDE
AnnounceDate2026-07-27
AnnouncementXMLSubmission_2026-07-27_02:42:37.239.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterRui Vitorino
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: NEWT:9606;
ModificationListamidated residue; iodoacetamide derivatized residue
InstrumentQ Exactive HF
Dataset History
RevisionDatetimeStatusChangeLog Entry
02026-01-05 12:16:16ID requested
12026-07-27 02:42:37announced
Publication List
10.3389/FPHAR.2026.1819323;
Keyword List
submitter keyword: None
Contact List
Joana Miranda
contact affiliationResearch Institute for Medicines (iMed.ULisboa), Faculty of Pharmacy, Universidade de Lisboa, Lisbon, Portugal rvitorino@ua.pt iBiMED- Department of Medical Siences University of Aveiro
contact emailjmiranda@ff.ulisboa.pt
lab head
Rui Vitorino
contact affiliationDepartment of Medical Sciences, Institute of Biomedicine iBiMED, University of Aveiro, Aveiro, Portugal
contact emailruimpvitorino@gmail.com
dataset submitter
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Dataset FTP location
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