Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans
Year: 2023
Type: article
Study design: Observational Study
Abstract: Diagnosis of drug-induced liver injury (DILI) and its distinction from other liver diseases are significant challenges in drug development and clinical practice. Here, we identify, confirm, and replicate the biomarker performance characteristics of candidate proteins in patients with DILI at onset (DO; n = 133) and follow-up (n = 120), acute non-DILI at onset (NDO; n = 63) and follow-up (n = 42), and healthy volunteers (HV; n = 104). Area under the receiver operating characteristic curve (AUC) for cytoplasmic aconitate hydratase, argininosuccinate synthase, carbamoylphosphate synthase, fumarylacetoacetase, fructose-1,6-bisphosphatase 1 (FBP1) across cohorts achieved near complete separation (range: 0.94-0.99) of DO and HV. In addition, we show that FBP1, alone or in combination with glutathione S-transferase A1 and leukocyte cell-derived chemotaxin 2, could potentially assist in clinical diagnosis by distinguishing NDO from DO (AUC range: 0.65-0.78), but further technical and clinical validation of these candidate biomarkers is needed.
Source: Nature Communications
Authors: Kodihalli C. Ravindra, Vishal S. Vaidya, Zhenyu Wang, Joel D. Federspiel, Richard Virgen-Slane, Robert A. Everley, Jane I. Grove, Camilla Stephens, Mireia F. Ocana, Mercedes Robles-Díaz, M. Isabel Lucena, Raul J. Andrade, Edmond Atallah, Alexander L. Gerbes, Sabine Weber, Helena Cortez-Pinto, Andrew J. Fowell, Hyder Hussaini, Einar S. Bjornsson, Janisha Patel, Guido Stirnimann, Sumita Verma, Ahmed M. Elsharkawy, William J. H. Griffiths, Craig Hyde, James W. Dear, Guruprasad P. Aithal, Shashi K. Ramaiah
Institutions: Pfizer (United States), Nottingham University Hospitals NHS Trust, University of Nottingham, Nottingham Biomedical Research Centre, Centro de Investigación Biomédica en Red de Enfermedades Hepáticas y Digestivas, Andalusian Centre for Nanomedicine and Biotechnology, Instituto de Investigación Biomédica de Málaga, Universidad de Málaga, LMU Klinikum, Ludwig-Maximilians-Universität München, University of Lisbon, Portsmouth Hospitals NHS Trust, Royal Cornwall Hospital Trust, Royal Cornwall Hospital, University of Iceland, National University Hospital of Iceland, University Hospital Southampton NHS Foundation Trust, University of Southampton, University of Bern, University Hospital of Bern, Brighton and Sussex Medical School, University Hospitals Sussex NHS Foundation Trust, Brighton and Sussex University Hospitals NHS Trust, University Hospitals Birmingham NHS Foundation Trust, Queen Elizabeth Hospital Birmingham, NIHR Birmingham Liver Biomedical Research Unit, NIHR Birmingham Biomedical Research Centre, Cambridge University Hospitals NHS Foundation Trust, The Queen's Medical Research Institute, University of Edinburgh
Language: English
Subfield: Pharmacology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $6,290
Awards: G4093197094, G5289873078, G5968716317
OpenAlex ID: W4323043065