Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans

作者：K. Ravindra, V. Vaidya, ZhenYu Wang, Joel D. Federspiel, Richard Virgen-Slane, R. Everley, J. Grove, C. Stephens, M. F. Ocaña, M. Robles-Díaz, M. Isabel Lucena, R. Andrade, Edmond Atallah, A. Gerbes, S. Weber, H. Cortez‐Pinto, A. Fowell, Hyder Hussaini, E. S. Bjornsson, J. Patel, G. Stirnimann, S. Verma, A. Elsharkawy, W. Griffiths, C. Hyde, J. Dear, G. Aithal, S. Ramaiah · 发表于：Nature Communications · 年份：2023 · DOI：10.1038/s41467-023-36858-6 · 被引用次数：34 · 研究领域：Medicine

Diagnosis of rare, unpredictable, drug-induced liver injury (DILI) is a significant challenge for patients, clinicians, and drug development. Here, the authors discover, evaluate, and validate potential blood biomarkers to diagnose DILI and distinguish it from alternative causes of liver injury. 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.