title: Clinical significance of the thymidylate synthase, dihydropyrimidine dehydrogenase, and thymidine phosphorylase mRNA expressions in hepatocellular carcinoma patients receiving 5-fluorouracil-based transarterial chemoembolization treatment.
abstract: OBJECTIVE
  To determine whether 5-fluorouracil (5-FU) sensitivity is associated with the mRNA expressions of thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), and thymidine phosphorylase (TP) in patients with hepatocellular carcinoma (HCC) treated with 5-FU-based transarterial chemoembolization (TACE).
  
  
  METHODS
  Formalin-fixed, paraffin-embedded tumor specimens from 40 patients treated with 5-FU-based TACE were selected for the examination of TS, DPD, and TP expression level by a quantitative real-time reverse transcription- polymerase chain reaction (PCR) technique. Patients were categorized into high and low expression groups according to the median expression level of each enzyme. Associations between the mRNA expression levels of TS, DPD, and TP and clinical parameters including treatment efficacies, clinicopathological factors, and prognosis were assessed.
  
  
  RESULTS
  High DPD expression was associated with worse treatment outcome, including intrahepatic disease progression rate (hazard ratio [HR] for high DPD versus low DPD, 2.212; 95% confidence interval [CI], 1.030-4.753; P = 0.042), extrahepatic disease progression rate (HR for high versus low DPD, 3.171; 95% CI, 1.003-10.023; P = 0.049), and progression-free survival (HR for high versus low DPD, 2.308; 95% CI, 1.102-4.836; P = 0.027). No correlation was found between the mRNA expression of TS/TP and treatment outcome.
  
  
  CONCLUSIONS
  DPD mRNA expression level was negatively correlated with the clinical outcomes of HCC patients treated with 5-FU-based TACE. These results provide indirect evidence that high DPD mRNA expression is a predictive marker of treatment resistance for 5-FU.
authors.affiliation: State Key Laboratory of Oncology in South China and National Anti-Cancer Drug Clinical Research Centre.
authors.forename: Hongyun
authors.initials: H
authors.lastname: Zhao
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Zhao
authors.forename: Ying
authors.initials: Y
authors.lastname: Guo
authors.forename: Yan
authors.initials: Y
authors.lastname: Huang
authors.forename: Suxia
authors.initials: S
authors.lastname: Lin
authors.forename: Cong
authors.initials: C
authors.lastname: Xue
authors.forename: Fei
authors.initials: F
authors.lastname: Xu
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.forename: Zhihuang
authors.initials: Z
authors.lastname: Hu
authors.forename: Li
authors.initials: L
authors.lastname: Zhang
keywords: 5-fluorouracil; dihydropyrimidine dehydrogenase; hepatocellular carcinoma; thymidine phosphorylase; thymidylate synthase; transarterial chemoembolization