⮝ Full datasets listing

PXD035024

PXD035024 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleBiomarkers of hepatocellular synthesis predict mortality in patients with decompensated cirrhosis
DescriptionBackground & 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.
HostingRepositoryPRIDE
AnnounceDate2023-11-20
AnnouncementXMLSubmission_2023-11-20_04:55:16.892.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterChristian Preisinger
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListacetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
InstrumentQ Exactive
Dataset History
RevisionDatetimeStatusChangeLog Entry
02022-06-30 07:00:32ID requested
12023-11-20 04:55:17announced
Publication List
10.1007/S12072-022-10473-X;
Keyword List
submitter keyword: Biomarker, Serum, Human, Cirrhosis, LC-MS/MS
Contact List
Pavel Strnad
contact affiliationMedical Department III, Gastroenterology, Metabolic diseases and Intensive Care, University Hospital RWTH Aachen, Aachen, Germany
contact emailpstrnad@ukaachen.de
lab head
Christian Preisinger
contact affiliationProteomics Facility, IZKF Aachen, University Clinic RWTH Aachen
contact emailcpreisinger@ukaachen.de
dataset submitter
Full Dataset Link List
Dataset FTP location
NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/11/PXD035024
PRIDE project URI
Repository Record List
[ + ]