PXD029576

PXD029576 is an original dataset announced via ProteomeXchange.

Title	Proteomics Indicates Lactate Dehydrogenase is Prognostic in Acetaminophen-induced Acute Liver Failure Patients and Reveals a Role for LKB1-AMPK Signaling
Description	Better biomarkers to predict death early in acute liver failure (ALF) are needed. To that end, we obtained early (study day 1) and later (day 3) serum samples from transplant-free survivors (n=28) and non-survivors (n=30) of acetaminophen (APAP)-induced ALF from the NIH-sponsored Acute Liver Failure Study Group, and from control volunteers (n=10). To identify proteins that increase early in serum during ALF, we selected individuals from this cohort for whom ALT was lower on day 1 than day 3, indicating a time point before the peak of injury (n=10/group). We then performed untargeted proteomics on their day 1 samples. Out of 1,682 quantifiable proteins, 79 were elevated ≥4-fold in ALF patients vs. controls and 23 of those were further elevated ≥4-fold in non-survivors vs. survivors, indicating potential to predict death. Interestingly, the biomarker with best performance was LDH. To confirm the prognostic potential of LDH, we measured activity in all day 1 and 3 samples from all 58 ALF patients. LDH was elevated in the non-survivors vs. survivors on both days. In addition, receiver operating characteristic (ROC) curve analyses revealed that LDH alone performed similarly to the model for end-stage liver disease (MELD), while a combination of MELD and LDH outperformed either alone. Finally, Upstream Analysis of our proteomics data indicated activation of LKB1-AMPK signaling in liver regeneration after APAP overdose and we confirmed that in mice. Overall, we conclude LDH can predict death in APAP-induced ALF and that LKB1-AMPK signaling may be a promising therapeutic target to improve survival.
HostingRepository	PRIDE
AnnounceDate	2022-08-12
AnnouncementXML	Submission_2022-08-12_00:00:58.035.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Stephanie Byrum
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Exploris 240

Revision	Datetime	Status	ChangeLog Entry
0	2021-11-04 10:17:51	ID requested
⏵ 1	2022-08-12 00:00:58	announced

Vazquez JH, Kennon-McGill S, Byrum SD, Mackintosh SG, Jaeschke H, Williams DK, Lee WM, Dranoff JA, McGill MR, Proteomics Indicates Lactate Dehydrogenase Is Prognostic in Acetaminophen-Induced Acute Liver Failure Patients and Reveals Altered Signaling Pathways. Toxicol Sci, 187(1):25-34(2022) [pubmed]

submitter keyword: Drug-induced liver injury, acute liver injury, liver regeneration, biomarkers

Michell R. McGill
contact affiliation	1Dept. of Pharmacology and Toxicology, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, AR 72205 2Dept. of Environmental and Occupational Health, Fay W. Boozman College of Public Health, University of Arkansas for Medical Sciences, Little Rock, AR 72205
contact email	mmcgill@uams.edu
lab head
Stephanie Byrum
contact affiliation	UAMS
contact email	sbyrum@uams.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD029576
     1. Label: PRIDE project
     2. Name: Proteomics Indicates Lactate Dehydrogenase is Prognostic in Acetaminophen-induced Acute Liver Failure Patients and Reveals a Role for LKB1-AMPK Signaling