Strong correlation between ASPM gene expression and HCV cirrhosis progression identified by co-expression analysis.

Hepatitis C virus (HCV) cirrhosis is at a high risk of hepatocellular carcinoma (HCC), and its progression is influenced by a complex network of gene interactions. A weighted gene co-expression network was constructed to identify gene modules associated with the seven-stage disease progression from HCV cirrhosis to HCV-related HCC (n=65). In the significant module (R2=0.86), a total of 25 network hub genes were identified, half of which were also hub nodes in the protein-protein interaction network of the module genes. In validation, most hub genes showed a moderate correlation with the disease progression, and only ASPM was highly correlated (R2=0.801). In the test set (n=63), ASPM was also more highly expressed in HCV cirrhosis with concomitant HCC than in those without HCC (P=0.0054). Gene set enrichment analysis (GSEA) demonstrated that the gene set of "regulation of protein amino acid phosphorylation" (n=20) was enriched in HCV cirrhosis samples with ASPM highly expressed (false discovery rate (FDR)=0.049). In gene ontology (GO) analysis, genes in the enriched set were associated with liver neoplasms and other neoplastic diseases. In conclusion, through co-expression analysis, ASPM was identified and validated in association with the progression of HCV cirrhosis probably by regulating tumor-related phosphorylation.