TY - JOUR
T1 - Tandem Mass Tag-Based Quantitative Proteomic Profiling Identifies Novel Serum Biomarkers of Drug-Induced Liver Injury in Humans
AU - Ravindra, Kodihalli C.
AU - Vaidya, Vishal S
AU - Wang, Zhenyu
AU - Federspiel, Joel D.
AU - Virgen-Slane, Richard
AU - Everley, Robert A.
AU - Grove, Jane I
AU - Stephens, Camilla
AU - Ocana, Mireia F.
AU - Robles-Díaz, Mercedes
AU - Lucena, M Isabel
AU - Andrade, Raul J
AU - Atallah, Edmond
AU - Gerbes, Alexander L.
AU - Weber, Sabine
AU - Cortez-Pinto, Helena
AU - Fowell, Andrew J.
AU - Hussaini, Hyder
AU - Bjornsson, Einar S.
AU - Patel, Janisha
AU - Stirnimann, Guido
AU - Verma, Sumita
AU - Elsharkawy, Ahmed M
AU - Griffiths, William J. H.
AU - Hyde, Craig
AU - Ramaiah, Shashi K.
AU - Dear, James W
AU - Aithal, Guruprasad P
N1 - © 2023. The Author(s).
PY - 2023/3/3
Y1 - 2023/3/3
N2 - 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.
AB - 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.
U2 - 10.1038/s41467-023-36858-6
DO - 10.1038/s41467-023-36858-6
M3 - Article
C2 - 36869085
SN - 2041-1723
VL - 14
SP - 1215
JO - Nature Communications
JF - Nature Communications
IS - 1
ER -