Kodihalli C. Ravindra
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; Lucena, M. Isabel; 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
Vishal S. Vaidya
Zhenyu Wang
Joel D. Federspiel
Richard Virgen-Slane
Robert A. Everley
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 Edmond.Atallah@nottingham.ac.uk
Clinical Research Fellow
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
GURUPRASAD AITHAL Guru.Aithal@nottingham.ac.uk
Professor of Hepatology
Shashi K. Ramaiah
Contributors
Kodihalli C. Ravindra
Researcher
Helena Cortez-Pinto
Researcher
GURUPRASAD AITHAL Guru.Aithal@nottingham.ac.uk
Researcher
James W. Dear
Researcher
Craig Hyde
Researcher
William J.H. Griffiths
Researcher
Ahmed M. Elsharkawy
Researcher
Sumita Verma
Researcher
Guido Stirnimann
Researcher
Janisha Patel
Researcher
Einar S. Bjornsson
Researcher
Hyder Hussaini
Researcher
Andrew J. Fowell
Researcher
Sabine Weber
Researcher
Vishal S. Vaidya
Researcher
Alexander L. Gerbes
Researcher
EDMOND ATALLAH Edmond.Atallah@nottingham.ac.uk
Researcher
Raul J. Andrade
Researcher
M Isabel Lucena
Researcher
Mercedes Robles-Díaz
Researcher
Mireia F. Ocana
Researcher
Camilla Stephens
Researcher
JANE GROVE jane.grove@nottingham.ac.uk
Researcher
Robert A. Everley
Researcher
Richard Virgen-Slane
Researcher
Joel D. Federspiel
Researcher
Zhenyu Wang
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. We used Tandem Mass Tag-labeled quantitative proteomics detecting 2323 proteins in a cohort comprising patients with DILI [at onset (DO) and follow-up (DF)], acute non-DILI [at onset (NDO) and follow-up (NDF)], and healthy volunteers (HV) to identify novel serum biomarkers. Thirteen candidates selected based on differential expression, liver-specific expression, and mechanistic relevance to liver pathology, were assessed in confirmatory and replication cohorts of HV (n=94), DO (n=123), DF (n=110), NDO (n=58) and NDF (n=37) using a targeted label-free SureQuant assay. Area under the receiver operating characteristic curve (AUC) ranging between 0.94 and 0.99 across cohorts for five of these biomarkers, reflected differentiation between DO and HV with high sensitivity and specificity. In addition, fructose-1,6-bisphosphatase 1 distinguished NDO from DO (AUC: 0.75 and 0.65) on its own or in combination with glutathione S-transferase A1 and leukocyte cell derived chemotaxin 2 (AUC: 0.78 and 0.68). These can potentially differentiate DILI and acute liver injury from non-drug etiologies.
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 8, 2023 |
Journal | Nature Communications |
Electronic ISSN | 2041-1723 |
Publisher | Nature Publishing Group |
Peer Reviewed | Peer Reviewed |
Volume | 14 |
Article Number | 1215 |
DOI | https://doi.org/10.1038/s41467-023-36858-6 |
Public URL | https://nottingham-repository.worktribe.com/output/15715090 |
Publisher URL | https://www.nature.com/articles/s41467-023-36858-6 |
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