Identification of potential targets with high centrality indicated by diethylnitrosamine plus thioacetamide-induced hepatocellular carcinoma model

Background and Aim: Hepatocellular carcinoma (HCC), a primary liver malignancy, represents a continuous challenge to clinicians as it is a leading cause of death due to cancer widely. Early detection is the only hope to cure patients from this deadly disease or possibly increase life expectancy. Mouse models are most acceptable studies as they have ability to manipulate their genome and transcriptome to evaluate mechanistic changes. In addition, system biology can improvise the understanding of molecular mechanism of HCC and also can reveal the protein hub involved in every stage of HCC. Materials and Methods: Herein, diethylnitrosamine and thioacetamide (TAA) were used to develop stage-specific HCC in Wistar rats. Histopathological changes, biochemical parameters, and the oxidative stress were measured in hepatocytes. We have reanalyzed the microarray dataset to identify the complex signaling pathways involved in hepatocarcino genesis induced by TAA. GSE45050 dataset was downloaded from Gene Expression Omnibus database, and the gene expression profile of nontumor, cirrhosis, and HCC was compared. Results: The study reveals stage-specific development of chronic HCC rat model and promising stage-specific targets (EHMT2, GMPS, and SPRY2) of HCC. \Conclusions: EHMT2, GMPS, and SPRY found as high centrality nodes in protein-protein interaction studies using high-throughput microarray data which tend to be present in signaling pathways and co-occur in a biological state of HCC. These genes can be targeted to understand the possible pathology, molecular changes, and target strategy under cirrhosis and HCC condition.

Automated summary

The study developed a stage-specific HCC rat model using diethylnitrosamine and thioacetamide (TAA) in Wistar rats, identifying promising stage-specific targets (EHMT2, GMPS, and SPRY2). Using high-throughput microarray data, EHMT2, GMPS, and SPRY were found to be high centrality nodes in protein-protein interaction studies, suggesting their potential role in signaling pathways of HCC.