  Chronic Hepatitis B (CHB) is an independent risk factor for hepatocellular
carcinoma (HCC) initiation without cirrhosis occurrence. Apart from the
favorable effects of some antiviral drugs following tumor resection on the
survival of HCC patients, the use of these agents is essential lifelong. Thus,
designing the target-oriented therapeutic strategies to increase life
expectancy in HCC patients would be very important. The present study aimed to
identify downregulated hub genes and enriched pathways in HB-related HCC using
a systems biology-based approach. Microarray data of GSE121248 were downloaded
from gene expression omnibus (GEO) database. The differentially expressed genes
(DEGs) with the cut-off criteria of adjusted p < 0.05 and Log Fold-change (FC)
< -1.5 were selected. Then, the genes with the highest centrality were
detected. Finally, the prognostic values of the hub genes were assessed. Six
under-expressed hub genes with the highest interaction degree, Betweenness and
Eigenvector centrality were including IGF-1, PTGS2, PLG, HGF, ESR-1 and CYP2B6.
Among genes with high centrality, several genes including CYP2C9, ESR-1, CXCL2,
CYP2C8, IGF-1, CYP3A4, CYP2E1, CERPINE-1 and PXR were prognostic in HCC. The
important repressed pathways were including metabolic pathways and PI3K-Akt and
chemokine signaling pathways. The under-expression of several genes implicated
in metabolism, differentiation and chemotaxis might be a hallmark of the
progression of HCC that can be considered as diagnostic and therapeutic
targets.
