Cytokinome profile evaluation in patients with hepatitis C virus infection

Abstract

The ''omics sciences'' (genomics, transcriptomics, proteomics) are often used to study living organisms as a whole system by evaluating the complex expression patterns of genes, miRNA, proteins, and metabolites. This study aimed, through bioinformatics and systems biology, to decipher the cytokinome profile in the evolution of inflammatory processes leading to cancer. The cytokinome was defined as the totality of cytokines and their interactions in and around biological cells. The system biology approach would provide a better understanding of the complex interaction network of cytokines, especially in cancer patients. Acquired knowledge would enable health providers with tools to evaluate disease onset through progression as well as identifying innovative therapeutic strategies. Understanding the role each cytokine plays in the metabolic network is of great importance. This paper reviews our group's ''omics'' work. In particular, it addresses the role cytokines play in liver disease in six different scenarios. The first is the role the cytokines play in chronic inflammatory diseases and cancers. The second is the significance of the cytokinome profile. The third is the role of liver cirrhosis as an inflammatory disease. The fourth is the comparison of cytokine levels evaluated in patients with chronic hepatitis C virus (HCV) or with HCV-related cirrhosis. The fifth is the comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of type 2 diabetes. And lastly, we present a comparison of cytokine levels evaluated in patients with HCV-related cirrhosis in the presence and absence of hepatocellular carcinoma.

Keywords: Cirrhosis; Cytokinome; Hepatitis C virus; Hepatocellular carcinoma; Interactome; Systems biology; Type 2 diabetes.

Figure 1

Relationship of the “omics sciences”, chronic inflammation, and cancer. The scheme shows (1) the necessity to integrate data derived from all the “omics sciences” for obtaining a complete picture of the system; and (2) the importance of including the cytokinome profile, at the proteomics level, due to the crucial role of cytokines in the chronic inflammation process leading to cancer.

Figure 2

Differences in the concentration (pg/mL) of significant cytokines, chemokines, and growth factors among hepatitis C virus, hepatitis C virus-related liver cirrhosis patients, and healthy controls. The mean concentrations, for each significant molecule, in healthy control subjects, HCV, and HCV-related LC patients were calculated using a t test. Healthy control - light grey; HCV patients - cyan, HCV-related LC patients - green bars. The cytokine expression was statistically different between HCV and HCV-related LC patients (^aP < 0.05). HCV: Hepatitis C virus; LC: Liver cirrhosis; IL: Interleukin; NGF: Nerve growth factor; HGF: Hepatocyte growth factor; MIF: Migration inhibitory factor.

Figure 3

Ingenuity pathway analysis of the significant molecules. The illustration shows the network of significant cytokines (green symbols), hub nodes (light blue symbols), and other involved molecules (white symbols) obtained by the ingenuity pathway analysis software. IL: Interleukin;HGF: Hepatocyte growth factor.