Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans.
Ravindra, Kodihalli C Vaidya, Vishal S Wang, Zhenyu Federspiel, Joel D Virgen-Slane, Richard Everley, Robert A Grove, Jane I Stephens, Camilla Ocana, Mireia F Robles-Díaz, Mercedes
Ravindra, Kodihalli C
Vaidya, Vishal S
Wang, Zhenyu
Federspiel, Joel D
Virgen-Slane, Richard
Everley, Robert A
Grove, Jane I
Stephens, Camilla
Ocana, Mireia F
Robles-Díaz, Mercedes
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2023-03-03
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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.
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Ravindra KC, Vaidya VS, Wang Z, Federspiel JD, Virgen-Slane R, Everley RA, Grove JI, Stephens C, Ocana MF, Robles-Díaz M, Isabel Lucena M, Andrade RJ, Atallah E, Gerbes AL, Weber S, Cortez-Pinto H, Fowell AJ, Hussaini H, Bjornsson ES, Patel J, Stirnimann G, Verma S, Elsharkawy AM, Griffiths WJH, Hyde C, Dear JW, Aithal GP, Ramaiah SK. Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans. Nat Commun. 2023 Mar 3;14(1):1215. doi: 10.1038/s41467-023-36858-6
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