Quantitative analysis of fluorouracil-related genes in chronic viral hepatitis using microdissection.
OBJECTIVE
Dihydropyrimidine dehydrogenase is the initial and rate-limiting enzyme in the catabolism of 5-fluorouracil. The aim of this study was to determine the levels of messenger RNA for 5-fluorouracil-related metabolic enzymes in cirrhotic liver and to assess the correlation between these mRNA levels and clinicopathological features.


METHODS
The study material consisted of 33 liver samples. The levels of mRNA for the 5- fluorouracil-related metabolic enzymes were quantified by real-time reverse transcription polymerase chain reaction combined with laser-captured microdissection.


RESULTS
The Dihydropyrimidine dehydrogenase mRNA level in patients with grade B liver damage was significantly lower than that in patients with grade A liver damage (p=0.009). The Dihydropyrimidine dehydrogenase and orotate phosphoribosyl transferase mRNA level in al samples was higher than that in a2 and a3 samples (p= 0.01 and 0.013, respectively). Statistically significant correlations were found between the hyaluronic acid and the thymidylate phosphorylase mRNA level (p= 0.0001), and the T-BIL and the dihydropyrimidine dehydrogenase mRNA level (p=0.01).


CONCLUSIONS
The level of Dihydropyrimidine dehydrogenase mRNA may be affected by the clinicopathological status of patients with cirrhosis.
Kakinuma
Daisuke
D
Department of Surgery, Nippon Medical School, Bunkyo-Ku, Tokyo, 113-8603, Japan. kdaisuke@nms.ac.jp
Yoshida
Hiroshi
H
Mamada
Yasuhiro
Y
Taniai
Nobuhiko
N
Mizuguchi
Yoshiaki
Y
Takahashi
Tsubasa
T
Shimizu
Tetsuya
T
Ishikawa
Yoshinori
Y
Akimaru
Koho
K
Naito
Zenya
Z
Tajiri
Takashi
T
D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics*; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005404:Fixatives; D005472:Fluorouracil / Q000493:pharmacokinetics*; D005557:Formaldehyde; D015870:Gene Expression / Q000235:genetics; D019694:Hepatitis B, Chronic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D019698:Hepatitis C, Chronic / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000473:pathology; D008103:Liver Cirrhosis / Q000201:enzymology / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D008111:Liver Function Tests; D008113:Liver Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D008297:Male; D042282:Microdissection / Q000379:methods; D008875:Middle Aged; D016612:Paraffin Embedding; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000964:Antimetabolites, Antineoplastic; D005404:Fixatives; D012333:RNA, Messenger; D005557:Formaldehyde; D042943:Dihydrouracil Dehydrogenase (NADP); D005472:Fluorouracil