PXD035024

PXD035024 is an original dataset announced via ProteomeXchange.

Title	Biomarkers of hepatocellular synthesis predict mortality in patients with decompensated cirrhosis
Description	Background & Aims: Since liver hepatocytes produce the majority of serum proteins, liver cirrhosis displays a massive alteration in serum proteome. The aim of the current study was to characterize these alterations and to study the prognostic usefulness of hepatocellular proteins available in routine clinical testing. Methods: Sera from 29 healthy controls and 43 cirrhotic subjects were subjected to untargeted proteomic analysis. The data were analyzed by Perseus program, R and unsupervised hierarchical clustering. The prognostic usefulness potential of selected biomarkers was tested in 61 controls and 285 cirrhotic individuals. Ingenuity pathway analysis (IPA) was employed to determine the upstream regulators that were further validated in 9 control and 9 cirrhotic livers. Results: Proteomics uncovered 65 down- and 16 upregulated hepatocellular serum proteins that are significantly down- respectively upregulated in cirrhotic subjects versus controls. Hierarchical clustering revealed two main clusters and 6 subclusters, while IPA identified HNF4α and IL6 as the two major upstream regulators that were confirmed in gene expression analyses. Pseudocholinesterase (AUROC 0.618; P=0.002), transferrin (AUROC 0.594; P=0.013), and transthyretin (TTR; AUROC 0.586; P=0.023) but not albumin serum levels discriminated between 90 days transplant-free survivors vs. non-survivors. Tree learning decision algorithm identified transthyretin as a biomarker that improved the prediction of death or transplant in the subset of patients with acute-on-chronic liver failure (ACLF). TTR≤58 mg/dl conferred an increased risk in both univariate (HR 1.75; 95% CI 1.14-2.67; P=0.01) and multivariable analysis (aHR 1.59; 95% CI 1.04-2.24; P=0.033). Conclusion: Our study uncovers the changes in hepatocellular serum proteins as well as the underlying transcriptional factors and suggest that transthyretin may constitute an useful prognostic adjunct in ACLF subjects.
HostingRepository	PRIDE
AnnounceDate	2023-11-20
AnnouncementXML	Submission_2023-11-20_04:55:16.892.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Christian Preisinger
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2022-06-30 07:00:32	ID requested
⏵ 1	2023-11-20 04:55:17	announced

10.1007/S12072-022-10473-X;

submitter keyword: Biomarker, Serum, Human, Cirrhosis, LC-MS/MS

Pavel Strnad
contact affiliation	Medical Department III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
contact email	pstrnad@ukaachen.de
lab head
Christian Preisinger
contact affiliation	Proteomics Facility, IZKF Aachen, University Clinic RWTH Aachen
contact email	cpreisinger@ukaachen.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD035024
     1. Label: PRIDE project
     2. Name: Biomarkers of hepatocellular synthesis predict mortality in patients with decompensated cirrhosis