Abstract
Application of network theory into biology revolutionarize the area by providing new method- ologies to observe complex biological systems. Networks are built based on the interaction between biological entities. Weigted topological overlap is a measure of connectivity and it is used in building biological networks by wTO method. Recently developed methodology of CoDiNA (Co-expression Differential Network Analysis) is used in comparison of gene co-expression networks in order to observe differences between such networks. This study aims at analysis of pathways and biological processes which take place in development of hepatocellular carcinoma from liver cirrhosis. Patients with liver cirrhosis have high risk of developing hepatocellular carcinoma. However, the mechanisms involved in development hepatocellular carcinoma from liver cirrhosis is unknown. The similarities and differences between hepatocellular carcinoma and liver cirrhosis are examined by comparing gene co- expression networks by wTO methodology. Comparison of networks are accomplished by use of CoDiNA. Tissue repair and regeneration processes are active in liver cirrhosis and hep- atocellular carcinoma due to injuries in liver tissue. Immune response is a part of tissue repair mechanisms. According to the results from the study, dysregulation of processes involved in tissue repair may be key mechanisms involved in evolution of hepatocellular carcinoma from liver cirrhosis. Effect of increase in immune response maintained by macrophages may be a causative of development of hepatocellular carcinoma since it further disrupts signaling pathways regulating stem cell maintenance in injury site. Such disruption may cause loss of control in stem cell maintenance which further contributes to tumorigenesis. Another finding from the study is that vitamin D deficiency might play role in triggering of carcinogenesis by affecting calcium signaling pathways. Moreover, RUNX2 is found as highly involved in mechanisms related to development of hepatocellular carcinoma. Regulation of macrophage activity may be experimentally tested in vivo as a part of potential therapeutic target to supress development of hepatocellular carcinoma from liver cirrhosis.