Dihydropyrimidine dehydrogenase gene expression in patients with hepatocellular carcinoma and metastatic liver cancer

Abstract

Objective: We studied dihydropyrimidine dehydrogenase (DPD) mRNA expression in patients with hepatocellular carcinoma (HCC) and metastatic liver cancer (Meta), and investigated the correlation between DPD activity and mRNA expression. Patients: Sixteen patients with hepatocellular carcinoma and eight patients with metastatic liver cancer (7 colorectal cancers and one breast cancer) were enrolled in this study. Method: The DPDmRNA expression was measured by real time reverse transcription polymerase chain reaction (Real Time RT-PCR), while DPD activity was measured using a radio enzymatic assay. Results: We investigated the correlation between DPD activity and mRNA expression, and a significant linear correlation was observed in the cancerous region (p<0.0001) and the non-cancerous region (p<0.01), in spite of differences in the tumor type. When comparing the DPDmRNA expression between the cancerous region and the non-cancerous region, no significant differences were observed in patients with HCC. However, in patients with Meta, the DPDmRNA expression in the non-cancerous region was significantly higher than that in the cancerous region (p<0.01). The DPDmRNA expression in the cancerous region was significantly higher in HCC patients than in Meta patients (p<0.05). On the other hand, the expression in the non-cancerous region was significantly higher in the Meta patients than in the HCC patients (p<0.05). Regarding the relationship between the clinical-pathological factors and the DPDmRNA expression, a significant correlation was observed between the DPDmRNA expression in the noncancerous region and the preoperative ICG R15 value (r=-0.559, p<0.01). The DPDmRNA expression decreased in patients with liver cirrhosis. These findings indicate that the DPDmRNA expression was influenced by liver function. Conclusion: We consider that 5-FU treatment will not be effective for tumors with a high DPD mRNA expression. Furthermore, adverse effects will easily occur in patients with liver damage. The DPDmRNA expression is considered to be a useful indicator for determining the suitability of chemotherapy in patients with liver cancer.