Systematic analysis of the gene expression in the livers of nonalcoholic steatohepatitis: implications on potential biomarkers and molecular pathological mechanism

Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD). The molecular pathological mechanism of NASH is poorly understood. Recently, high throughput data such as microarray data together with bioinformatics methods have become a powerful way to identify bi...

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Veröffentlicht in:PloS one 2012-12, Vol.7 (12), p.e51131-e51131
Hauptverfasser: Zhang, Yida, Baker, Susan S, Baker, Robert D, Zhu, Ruixin, Zhu, Lixin
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Zhu, Ruixin
Zhu, Lixin
description Non-alcoholic steatohepatitis (NASH) is a severe form of non-alcoholic fatty liver disease (NAFLD). The molecular pathological mechanism of NASH is poorly understood. Recently, high throughput data such as microarray data together with bioinformatics methods have become a powerful way to identify biomarkers and to investigate pathogenesis of diseases. Taking advantage of well characterized microarray datasets of NASH livers, we performed a systematic analysis of potential biomarkers and possible pathological mechanism of NASH from a bioinformatics perspective.CodeLink Human Whole Genome Bioarrays were analyzed to find differentially expressed genes (DEGs) between controls and NASH patients. Four methods were used to identify DEGs and the intersection of DEGs identified by these methods was subsequently used for both biomarker prediction and molecular pathological mechanism analysis. For biomarker prediction, rank aggregation was used to rank DEGs identified by all these methods according to their significance of different expression. Alcohol dehydrogenase 4 (ADH4) exhibited the highest rank suggesting the most significant differential expression between normal and disease condition. Together with the previous report demonstrating the association between ADH4 and the pathogenesis of NASH, our data suggest that ADH4 could be a potential biomarker for NASH. For molecular pathological mechanism analysis, two clusters of highly correlated annotation terms and genes in these terms were identified based on the intersection of DEGs. Then, pathways enriched with these genes were identified to construct the network. Using this network, both for the first time, amino acid catabolism is implicated to play a pivotal role and urea cycle is implicated to be involved in the development of NASH.The results of our study identified potential biomarkers and suggested possible molecular pathological mechanism of NASH. These findings provide a comprehensive and systematic understanding of the pathogenesis of NASH and may facilitate the diagnosis, prevention and treatment of NASH.
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Alcohol dehydrogenase 4 (ADH4) exhibited the highest rank suggesting the most significant differential expression between normal and disease condition. Together with the previous report demonstrating the association between ADH4 and the pathogenesis of NASH, our data suggest that ADH4 could be a potential biomarker for NASH. For molecular pathological mechanism analysis, two clusters of highly correlated annotation terms and genes in these terms were identified based on the intersection of DEGs. Then, pathways enriched with these genes were identified to construct the network. Using this network, both for the first time, amino acid catabolism is implicated to play a pivotal role and urea cycle is implicated to be involved in the development of NASH.The results of our study identified potential biomarkers and suggested possible molecular pathological mechanism of NASH. 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The molecular pathological mechanism of NASH is poorly understood. Recently, high throughput data such as microarray data together with bioinformatics methods have become a powerful way to identify biomarkers and to investigate pathogenesis of diseases. Taking advantage of well characterized microarray datasets of NASH livers, we performed a systematic analysis of potential biomarkers and possible pathological mechanism of NASH from a bioinformatics perspective.CodeLink Human Whole Genome Bioarrays were analyzed to find differentially expressed genes (DEGs) between controls and NASH patients. Four methods were used to identify DEGs and the intersection of DEGs identified by these methods was subsequently used for both biomarker prediction and molecular pathological mechanism analysis. For biomarker prediction, rank aggregation was used to rank DEGs identified by all these methods according to their significance of different expression. Alcohol dehydrogenase 4 (ADH4) exhibited the highest rank suggesting the most significant differential expression between normal and disease condition. Together with the previous report demonstrating the association between ADH4 and the pathogenesis of NASH, our data suggest that ADH4 could be a potential biomarker for NASH. For molecular pathological mechanism analysis, two clusters of highly correlated annotation terms and genes in these terms were identified based on the intersection of DEGs. Then, pathways enriched with these genes were identified to construct the network. Using this network, both for the first time, amino acid catabolism is implicated to play a pivotal role and urea cycle is implicated to be involved in the development of NASH.The results of our study identified potential biomarkers and suggested possible molecular pathological mechanism of NASH. These findings provide a comprehensive and systematic understanding of the pathogenesis of NASH and may facilitate the diagnosis, prevention and treatment of NASH.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23300535</pmid><doi>10.1371/journal.pone.0051131</doi><tpages>e51131</tpages><oa>free_for_read</oa></addata></record>
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subjects ADH4 protein
Alcohol dehydrogenase
Alcoholic beverages
Alcoholism
Amino acids
Analysis
Annotations
Bioindicators
Bioinformatics
Biological markers
Biology
Biomarkers
Biomarkers - metabolism
Biopsy
Catabolism
Cluster analysis
Computational Biology
Correlation analysis
Dehydrogenases
Diabetes
DNA microarrays
Ethanol
Fatty acids
Fatty liver
Fatty Liver - genetics
Fatty Liver - pathology
Gene expression
Gene Expression Profiling
Genes
Genetic research
Genomes
Hepatitis
Hepatology
Humans
Identification methods
Lipids
Liver
Liver cancer
Liver diseases
Medical research
Medicine
Metabolism
Non-alcoholic Fatty Liver Disease
Nutrition
Obesity
Oligonucleotide Array Sequence Analysis
Oxidative stress
Pathogenesis
Pathology, Molecular
Pediatrics
Real-Time Polymerase Chain Reaction
Reverse Transcriptase Polymerase Chain Reaction
RNA, Messenger - genetics
Rodents
Signal Transduction
Studies
Type 2 diabetes
Urea
title Systematic analysis of the gene expression in the livers of nonalcoholic steatohepatitis: implications on potential biomarkers and molecular pathological mechanism
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