Tandem Mass Tag-Based Quantitative Proteomic Profiling Identifies Novel Serum Biomarkers of Drug-Induced Liver Injury in Humans

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 PatelGuido Stirnimann, Sumita Verma, Ahmed M Elsharkawy, William J. H. Griffiths, Craig Hyde, Shashi K. Ramaiah, James W Dear, Guruprasad P Aithal

Research output: Contribution to journalArticlepeer-review

Abstract / Description of output

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.

Original languageEnglish
Pages (from-to)1215
JournalNature Communications
Volume14
Issue number1
DOIs
Publication statusPublished - 3 Mar 2023

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