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Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans
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| Title: | Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans |
| Author: |
... 18 more authors Show all authors |
| Date: | 2023-03-03 |
| Language: | English |
| Scope: | 2966107 |
| Department: | Other departments Faculty of Medicine |
| Series: | Nature Communications; 14(1) |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-023-36858-6 |
| Subject: | Meltingarlæknisfræði; Humans; Proteomics; Chemical and Drug Induced Liver Injury; Argininosuccinate Synthase; Biomarkers; CD8 Antigens; Fructose; Multidisciplinary; General Physics and Astronomy; General Chemistry; General Biochemistry,Genetics and Molecular Biology |
| URI: | https://hdl.handle.net/20.500.11815/4161 |
Citation:Ravindra , K C , Vaidya , V S , Wang , Z , Federspiel , J D , Virgen-Slane , R , Everley , R A , Grove , J I , Stephens , C , Ocana , M F , Robles-Díaz , M , Isabel Lucena , M , Andrade , R J , Atallah , E , Gerbes , A L , Weber , S , Cortez-Pinto , H , Fowell , A J , Hussaini , H , Björnsson , E S , Patel , J , Stirnimann , G , Verma , S , Elsharkawy , A M , Griffiths , W J H , Hyde , C , Dear , J W , Aithal , G P & Ramaiah , S K 2023 , ' Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans ' , Nature Communications , vol. 14 , no. 1 , 1215 , pp. 1215 . https://doi.org/10.1038/s41467-023-36858-6
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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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Description:Funding Information: K.C.R., V.S.V., Z.W., J.D.F., V.S.R., R.E., M.F.O., C.H., and S.K.R. are employed by Pfizer. G.P.A. has served as a consultant and an advisory board member for Pfizer Inc, Inventiva Pharma, GlaxoSmithKline and KaNDy Therapeutics; he has been a consultant to BerGenBio ASA, Median Technologies, FRACTYL, Amryt Pharmaceuticals and AstraZeneca; and has given presentations on behalf of Roche Diagnostics and Medscape. A.G.: stockholder MetaHeps GmbH and owner of IP. E.S.B. is a member of the hepatic safety committee for Galmed pharmaceuticals in the Armor study. H.C.P. lectures and advisory board fees from Intercept, Orphalan, Novo Nordisk, Roche Portugal and EISAI. S.V. has served as a consultant for Abbvie and Gilead Sciences, and given presentations on behalf of Gilead Sciences, Abbvie and Dr Falk. J.W.D. is the Chief Investigator on the ALBATROSS and POP Trials funded by Egetis Therapeutics. A.J.F. is a consultant and advisory board member for Gilead Sciences, Dr Falk Pharma and Accelerated Enrollment Solutions and has given presentations on behalf of Intercept Pharmaceuticals. A.M.E. has been a consultant for GSK, SOBI and Gilead. The remaining authors declare no competing interests. Funding Information: We thank all our study participants and research study teams for their involvement in providing resources for this research. This article is supported by the members of COST Action “CA17112 - Prospective European Drug-Induced Liver Injury Network” supported by COST (European Cooperation in Science and Technology), www.cost.eu including J.I.G., C.S., M.R.-D., M.I.L., R.J.A., E.A., A.L.G., S.W., H.C.-P., E.S.B., G.S. and G.P.A. We acknowledge support from the members of the PRO-EURO-DILI Network for input on aligning protocols across multiple centers as well as in the case adjudication. We acknowledge Melanie Lingaya, Ryan Criswell, Deborah Hart, James Stejskal, Richard Giovanelli, Kelly Fader, and Heather Llewellyn for their assistance with sample processing. Funding was made available from the Drug Safety Research and Development department within Pfizer’s Worldwide Research Development and Medical. J.I.G., E.A., and G.P.A. are supported by NIHR Nottingham Biomedical Research Centre [BRC-1215-20003]. The views expressed are those of the authors and not necessarily those of the National Health Service (NHS), the NIHR or the Department of Health. Publisher Copyright: © 2023, The Author(s).
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