The results of this study, together with our previous finding that there is a negative correlation between SPRED2 expression levels and cancer grades in HCC, further support the hypotheses that a reduction in or loss of SPRED2 expression in hepatocytes contributes to the initiation and development of HCC, and that SPRED2 serves as a potential biomarker for HCC. This evidence concerns the gene SPRED2 and hepatocellular carcinoma.