Clinical trial of GPC3 and AKR1B10 as the novel serum marker for hepatocellular carcinoma

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GPC3 and AKR1B10 were identified as candidate genes for hepatocelular carcinoma (HCC) by comprehensive expression analysis. In this study, we demonstrated that expression levels of both GPC3 and AKR1B10 in HCC by immunohistochemistry were correlated with those of serum obtained from HCC patients. Besides, we measured serum GPC3 levels from HCC patients after surgery and found that GPC3 levels were changed in accordance with relapse and the state after therapy. Furthermore, we observed that serum GPC3 levels of about 10% of patients undergoing hepatectomy were not recovered to normal range, whose recurrence rate were significantly high. On the other hand, we also investigated copy number analysis using single nucleotide polymorphism arrays and found that expression levels and copy number were significantly correlated, indicating that gene expression are subject to the chromosomal bias. As for gene therapy, we found that anti-GPC3 monoclonal antibody we established harbors anti-tumor effects, which was confirmed in vivo. We also observed that AKR1B10 would enhance the anti-tumor effect of adriamycin for HCC by siRNA experiments using nude mice to whom hepatoma cell line, PLC/PRF/5 cells were transplanted. Through these results, we hope that GPC3 and AKR1b10 are the candidate for gene therapy.