UBE2T and CYP3A4: Hub Genes Regulating the Transformation of Cirrhosis into Hepatocellular Carcinoma

Cirrhosis is the primary driver of hepatocellular carcinoma (HCC). Blocking the deterioration of cirrhosis into HCC would be of benefit for long-term survival. We applied a series of bioinformatic online databases to select and analyze the hub genes concerning cirrhosis and HCC, and identified UBE2T and CYP3A4 as hub genes for cirrhosis-HCC transformation. An elevated UBE2T and a decreased CYP3A4 were expressed in HCC compared with cirrhosis, which have been confirmed by real-time polymerase chain reaction (RT-PCR), Western Blotting (WB) and immunohistochemistry (IHC). The specificity (89.9%) and sensitivity (74.1%) on the combination of UBE2T and CYP3A4 for predicting HCC development in cirrhosis patients were better than that of UBE2T or CYP3A4 alone, or alpha-fetoprotein. The effectiveness of the combination of UBE2T and CYP3A4 was further verified by 15 paired HCC and paracancerous cirrhosis samples using RT-PCR, with a specificity of 100% and a sensitivity of 80%. HCC patients with elevated UBE2T and decreased CYP3A4 expression demonstrated a poorer overall survival rate (P = 0.0016, 0.019) and disease-free survival rate (P = 0.0013, 0.041). In conclusion, UBE2T and CYP3A4 could be a new combination of biomarkers for the carcinogenesis and progression of cirrhosis into HCC.