Investigation of potential molecular biomarkers and small molecule drugs for hepatocellular carcinoma transformed from cirrhosis.

Abstract

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors in China and the third leading cause of cancer-associated morality. The aim of the present study was to investigate and analyze differentially-expressed genes (DEGs) between cirrhosis and HCC, in order to screen the key genes involved in the transformation from cirrhosis to HCC and provide novel targets for the diagnosis and treatment of HCC in patients with cirrhosis. The gene expression profile, GSE17548, was obtained from Gene Expression Omnibus database and the DEGs were identified by LIMMA package in R language. Kyoto Encyclopedia of Genes and Genomes and gene ontology biology process analysis were performed for the DEGs. Differential co-expression network (DEN) analysis was conducted and the network was visualized using Cytoscape. Small molecule drugs were also screened from the Comparative Toxicogenomics Database for higher degree DEGs. A total of 95 DEGs were obtained, including 46 upregulated and 49 downregulated genes. The upregulated DEGs were primarily involved in biological processes and pathways associated with the cell cycle, while the downregulated DEGs were primarily involved in immune-associated biological processes. A total of 22 key DEGs were identified by DEN analysis, which distinguished HCC from cirrhosis samples. Furthermore, estradiol, benzo(a)pyrene, acetaminophen, copper sulfate and bisphenol A were identified as the five most associated chemicals to these 22 DEGs. In conclusion, the hub genes and chemicals identified by the present study may provide a theoretical basis for additional research on diagnosis and treatment of HCC transformed from cirrhosis.