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Series GSE139602 Query DataSets for GSE139602
Status Public on Sep 11, 2021
Title Molecular characterization of chronic liver disease dynamics: from liver fibrosis to acute-on-chronic liver failure
Organism Homo sapiens
Experiment type Expression profiling by array
Summary BACKGROUND: The molecular mechanisms driving the progression from early chronic liver disease (eCLD) to cirrhosis and, finally, acute-on-chronic liver failure (ACLF) are largely unknown. Thus, the aim of this work is to develop a network-based approach to investigate molecular pathways driving progression from eCLD to ACLF. We created 9 liver-specific biological networks capturing key pathophysiological processes potentially related to CLD. We used these networks as framework to perform gene set enrichment analyses(GSEA) and create dynamic profiles of disease progression. RESULTS: Principal component analyses revealed that samples clustered according to the disease stage. GSEA analyses of the defined processes showed an up-regulation of inflammation, fibrosis and apoptosis networks throughout disease progression. Interestingly, we did not find significant gene expression differences between CC and DC, while ACLF showed acute expression changes in all the defined liver-related networks. The analyses of disease progression patterns identified ascending and descending expression profiles associated to ACLF onset. Functional analyses showed that ascending profiles were associated to inflammation, fibrosis, apoptosis, senescence and carcinogenesis networks, while descending profiles were mainly related to oxidative stress and genetic factors. We confirmed by qPCR the up-regulation of 4 genes of the ascending profile CXCL-6, KRT-18, SPINK-1, and ITGA2, and validated our findings on an independent patient’s cohort. CONCLUSION: ACLF is characterized by a specific hepatic gene expression pattern related to inflammation, fibrosis, apoptosis, senescence and carcinogenesis processes. Moreover, the observed profile is significantly different from that of compensated and decompensated cirrhosis, supporting thus the hypothesis that ACLF should be considered a distinct entity.
 
Overall design Transcriptome analysis on liver biopsies from patients at different liver disease stages, including 5 fibrosis(eCLD), 8 compensated cirrhosis, 12 decompensated cirrhosis, 8 ACLF, and 6 control healthy livers was performed.
 
Contributor(s) Graupera I, Isus L, Lozano JJ, Sancho-Bru P, Ginès P, Aloy P
Citation(s) 35540106
Submission date Oct 30, 2019
Last update date Sep 22, 2022
Contact name Juanjo Lozano
E-mail(s) juanjo.lozano@ciberehd.org
Organization name CIBEREHD
Department Plataforma de Bioinformatica
Street address C/ Rosselló 153
City Barcelona
ZIP/Postal code 08036
Country Spain
 
Platforms (1)
GPL13667 [HG-U219] Affymetrix Human Genome U219 Array
Samples (39)
GSM4144550 Healthy Liver biopsy (LMS1)
GSM4144551 Healthy Liver biopsy (LMS2)
GSM4144552 Healthy Liver biopsy (LMS3)
Relations
BioProject PRJNA580468

Download family Format
SOFT formatted family file(s) SOFTHelp
MINiML formatted family file(s) MINiMLHelp
Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE139602_RAW.tar 81.9 Mb (http)(custom) TAR (of CEL)
Processed data included within Sample table
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