Skip to main content

Research Repository

Advanced Search

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; Isabel Lucena, M.; Andrade, Raul J.; Atallah, Edmond; Gerbes, Alexander L.; Weber, Sabine; Cortez-Pinto, Helena; Fowell, Andrew J.; Hussaini, Hyder; Bjornsson, Einar S.; Patel, Janisha; Stirnimann, Guido; Verma, Sumita; Elsharkawy, Ahmed M.; Griffiths, William J. H.; Hyde, Craig; Dear, James W.; Aithal, Guruprasad P.; Ramaiah, Shashi K.

Authors

Kodihalli C. Ravindra

Vishal S. Vaidya

Zhenyu Wang

Joel D. Federspiel

Richard Virgen-Slane

Robert A. Everley

Profile Image

JANE GROVE jane.grove@nottingham.ac.uk
Assistant Professor

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 Patel

Guido Stirnimann

Sumita Verma

Ahmed M. Elsharkawy

William J. H. Griffiths

Craig Hyde

James W. Dear

Shashi K. Ramaiah



Contributors

Kodihalli C. Ravindra
Researcher

Vishal S. Vaidya
Researcher

Zhenyu Wang
Researcher

Joel D. Federspiel
Researcher

Richard Virgen-Slane
Researcher

Robert A. Everley
Researcher

Camilla Stephens
Researcher

Mireia F. Ocana
Researcher

Mercedes Robles-Díaz
Researcher

M Isabel Lucena
Researcher

Raul J. Andrade
Researcher

Edmond Atallah
Researcher

Alexander L. Gerbes
Researcher

Sabine Weber
Researcher

Helena Cortez-Pinto
Researcher

Andrew J. Fowell
Researcher

Hyder Hussaini
Researcher

Einar S. Bjornsson
Researcher

Janisha Patel
Researcher

Guido Stirnimann
Researcher

Sumita Verma
Researcher

Ahmed M. Elsharkawy
Researcher

William J.H. Griffiths
Researcher

Craig Hyde
Researcher

James W. Dear
Researcher

Shashi K. Ramaiah
Researcher

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.

Citation

Ravindra, K. C., Vaidya, V. S., Wang, Z., Federspiel, J. D., Virgen-Slane, R., Everley, R. A., …Ramaiah, S. K. (2023). Tandem mass tag-based quantitative proteomic profiling identifies candidate serum biomarkers of drug-induced liver injury in humans. Nature Communications, 14, Article 1215. https://doi.org/10.1038/s41467-023-36858-6

Journal Article Type Article
Acceptance Date Dec 22, 2022
Online Publication Date Mar 3, 2023
Publication Date Mar 3, 2023
Deposit Date Jan 5, 2023
Publicly Available Date Mar 28, 2024
Journal Nature Communications
Electronic ISSN 2041-1723
Publisher Springer Science and Business Media LLC
Peer Reviewed Peer Reviewed
Volume 14
Article Number 1215
DOI https://doi.org/10.1038/s41467-023-36858-6
Keywords General Physics and Astronomy; General Biochemistry, Genetics and Molecular Biology; General Chemistry; Multidisciplinary
Public URL https://nottingham-repository.worktribe.com/output/15715090
Publisher URL https://www.nature.com/articles/s41467-023-36858-6
Additional Information Received: 2 June 2022; Accepted: 16 February 2023; First Online: 3 March 2023; : 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.

Files




You might also like



Downloadable Citations