A twenty gene-based gene set variation score reflects the pathological progression from cirrhosis to hepatocellular carcinoma

Abstract

The molecular mechanism of the pathological progression from cirrhosis to hepatocellular carcinoma (HCC) remains elusive. In the present study, tissue samples from normal liver, cirrhosis and HCC were subjected to differentially gene expression analysis, weighted gene correlation network analysis to identify the twenty hub genes (TOP2A, CDC20, PTTG1, CDCA5, CCNB2, PRC1, KIF20A, SF3B4, HSP90AB1, FOXD2, PLOD3, CCT3, SETDB1, VPS45, SPDL1, RACGAP1, MED24, KIAA0101, ZNF282, and USP21) in the pathological progression from cirrhosis to HCC. Each sample was calculated a hub gene set variation analysis (HGSVA) score using Gene Set Variation Analysis, The HGSVA score significantly increased with progression from cirrhosis to HCC, and this result was validated in two independent data sets. Moreover, this score may be used as a blood-based marker for HCC and is an independent prognostic factor of recurrence-free survival (RFS) and overall survival (OS). High expression of the hub genes may be driven by hypomethylation. The twenty gene-based gene set variation score may reflect the pathological progression from cirrhosis to HCC and is an independent prognostic factor for both OS and RFS.