Expression of cystathionine β-synthase is downregulated in hepatocellular carcinoma and associated with poor prognosis

The cystathionine β-synthase (CBS) gene encodes an enzyme that catalyzes the synthesis of cystathionine in the trans-sulfuration pathway and is subject to tight regulation because of its critical role in antioxidant and methylation metabolism. The expression level of CBS in 120 hepatocellular carcinoma (HCC) specimens evaluated by real-time reverse transcriptase PCR (RT-PCR) is markedly lower than in surrounding non-cancerous liver (P<0.0001). The correlation between CBS gene expression in HCC and clinicopathological parameters or survival of HCC patients was statistically analyzed in the present study. Our study demonstrated that reduced CBS expression is significantly correlated with high tumor stage (P=0.0019), high Edmondson grade (P=0.00084), and high AFP level (P=6.2x10−5). Interestingly, a survival analysis showed that a significantly shorter overall survival (OS) time is observed in patients with reduced CBS expression (P=0.0022), although CBS expression was determined not to be an independent prognostic factor for OS (P=0.071) after considering tumor stage, tumor size, and AFP level. However, for the 62 patients with low AFP levels (<100 ng/ml), reduced CBS expression was found to be an independent prognostic factor for OS (P=0.0042) after considering tumor stage and tumor size. Thus, the expression level of CBS mRNA could be useful to predict clinical outcome of HCC, especially for patients with low AFP levels.