Significance of dihydropyrimidine dehydrogenase and thymidylate synthase mRNA expressions in hepatocellular carcinoma

Aim: The significance of dihydropyrimidine dehydrogenase (DPD) and thymidylate synthase (TS) gene expressions for the post-surgical prognosis of hepatocellular carcinoma (HCC) has not yet been determined. In the present study, we clarified the significance of DPD and TS gene expressions for the prognosis of HCC. Methods: Seventy-four patients, who underwent curative hepatic resection for primary HCC, were evaluated. The DPD and TS mRNA levels of the resected HCC specimens were evaluated using a microdissection technique and quantative real-time RT-PCR. The patients were categorized into high and low groups for each mRNA based on the median value. Various clinicopathological factors, including prognosis, and proliferation index using Ki-67 staining were evaluated in association with the DPD and TS mRNA expression levels. Results: The low DPD mRNA expression was related to younger age, advanced clinical stage, undifferentiated histology, and microscopic intrahepatic metastasis. The overall and recurrence-free survival were significantly lower in the low DPD group than in the high DPD group (P < 0.05). Furthermore, the proliferation index in the low DPD group was significantly higher than that in the high DPD group (P < 0.01). On the other hand, the high TS group showed a tendency of better prognosis than the low TS group, although it was not statistically significant. Conclusions: The low DPD mRNA expression is a significant poor prognostic factor. after curative resection of HCC.