COMMON GENETIC ASPECTS BETWEEN HEPATITIS B/C AND CIRRHOSIS: A NETWORK-BASED APPROACH USING GENE EXPRESSION DATA

Abstract

Hepatitis B and C viruses (HBV and HCV) are major global burdens in liver disease and frequently progress to complications of cirrhosis. In this study, the common genetic characteristics with the development of cirrhosis associated with HBV/HCV infections were systematically investigated using a network based approach with a wealth of gene expression data. In this work, we integrated transcriptomic profiles from infected as well cirrhotic tissues using GEO datasets,  GSE121248, GSE55092, GSE89377 and GSE139602. A total of 47  common upregulated genes; involvement in the progression of both HBV and HCV infections as well as cirrhosis, were identified through this analysis. Using R programming, we explored the biological meaning of this group of genes related to the pathways and gene ontologies. To find key hub genes and essential modules of a PPI network, we built a PPI network by using the STRING Cytoscape plugin. We identified 10 hub genes (CDC20, CCNB2, MELK, AURKA, PRC1, TOP2A, CDCA5, PTTG1, TYMS and UBE2C) which might act as important mediators in the modulation of effects of HBV and HCV infections in the development of cirrhosis. Additionally, interaction networks were also developed for transcription factors (TFs) – TFs – miRNA and drug interactions in  the NetworkAnalyst platform. The systems biology approach in the study of structure and function of molecular complexes in the hepatitis related liver disease stresses the complexity of the mechanisms and significance of the approach to unravel it. We specify the hub genes as a potential target for therapeutics for future disease modulation study, but re validation of their role in disease modulation is necessary based on further research before application.