• Screening of key biomarkers and biological processes in liver cirrhosis: Evidence based on systems biology analysis
  • Sedigheh Behrouzifar,1,*
    1. Department of Medical Sciences, Shahrood Branch, Islamic Azad University, Shahrood, Iran.


  • Introduction: Liver cirrhosis develops as a result of chronic hepatitis. At present, there are not effective strategies to treat liver cirrhosis, partially due to a poor understanding of the molecular mechanisms leading to cirrhosis. The present study aimed to screen key biomarkers and biological processes involved in liver cirrhosis based on systems biology analysis.
  • Methods: Microarray dataset GSE164760 was downloaded from the Gene Expression Omnibus (GEO) database, which including 8 cirrhotic samples and 6 healthy samples. The differentially expressed genes(DEGs) (adjusted p-value<0.05) was computed using R studio software. Protein-protein interaction network(PPI) was constructed by STRING database. Hub genes were selected by Geghi software. Gene ontology (GO) and KEGG pathway enrichment analysis of DEGs were performed with Enrichr web server.
  • Results: Seven key hub genes were identified with degree>=14, which were FETUB, FTCD, AMBP, AGXT, COL3A1, F2 and CXCL8. GO analysis showed that DEGs (304 genes) were mainly enriched in biological processes such as extracellular structure organization (GO:0043062, combined score=949.3), negative regulation of blood coagulation (GO:0030195, combined score=10681.5), positive regulation of neutrophil chemotaxis (GO:0090023, combined score= 3855.5) and cellular amino acid catabolic process (GO:0009063, combined score=2962.4). KEGG pathway analysis showed that up-regulated genes were mainly enriched in Focal adhesion(combined score= 677.2), Cytokine-cytokine receptor interaction (combined score=704.7) and Antigen processing and presentation(combined score=2535.3). Down-regulated genes were mainly enriched in Glycine, serine and threonine metabolism(combined score=6651.8), Complement and coagulation cascades(combined score=4718.09) and arachidonic acid metabolism(combined score=775.2).
  • Conclusion: In liver cirrhosis the genes involved in amino acid and fatty acid metabolism and coagulation were under-expressed and genes related to collagen synthesis and inflammation were over-expressed that can be noticed as diagnostic and therapeutic targets.
  • Keywords: liver cirrhosis, Hub genes, Gene ontology, systems biology