Levels and expressions of orotate phosphoribosyltransferase in gastric carcinoma and normal gastric mucosa tissues.
BACKGROUND
Orotate phosphoribosyltransferase (OPRT; EC 2.4.2.10), a key enzyme that catalyzes one of the primary steps in the phosphorylation of fluoropyrimidine, was recently recognized as an important enzyme that determines the anticancer effects of the dihydropyrimidine dehydrogenase-inhibitory fluoropyrimidine, S-1.


METHODS
Levels of OPRT were examined in 97 gastric carcinoma tissues and 65 normal gastric mucosa tissues obtained from patients with gastric carcinoma. The relation between OPRT levels and clinicopathological variables was evaluated, and correlations of OPRT with thymidylate synthase and dihydropyrimidine dehydrogenase levels in gastric carcinoma tissues were evaluated.


RESULTS
Although OPRT levels were high in well-differentiated and localized carcinomas, they were not correlated with other clinicopathological variables or with the pathological stage of gastric carcinoma. Levels of OPRT were significantly higher in gastric carcinoma tissue than in normal gastric mucosa. OPRT levels were not correlated with levels of either thymidylate synthase or dihydropyrimidine dehydrogenase. In samples of gastric carcinoma tissues and normal gastric mucosa tissues obtained simultaneously from 24 patients, no correlation was found between OPRT levels in gastric carcinoma and levels in normal gastric mucosa.


CONCLUSIONS
These results suggest that the OPRT level is significantly higher in gastric carcinoma tissue than in normal gastric mucosa and that the OPRT level in gastric carcinoma is a novel variable that is independent of the levels of other previously known enzymes related to 5-fluorouracil (FU) metabolism.
Sakurai
Yoichi
Y
Department of Surgery, Fujita Health University School of Medicine, 1-98 Dengakugakubo Kutsukake-cho, Toyoake, 470-1192, Japan.
Kamoshida
Shingo
S
Furuta
Shinpei
S
Sunagawa
Risaburo
R
Inaba
Kazuki
K
Isogaki
Jun
J
Komori
Yoshiyuki
Y
Uyama
Ichiro
I
Tsutsumi
Yutaka
Y
D000230:Adenocarcinoma / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000368:Aged; D000964:Antimetabolites, Antineoplastic / Q000493:pharmacokinetics; D042943:Dihydrouracil Dehydrogenase (NADP) / Q000378:metabolism; D005260:Female; D005472:Fluorouracil / Q000493:pharmacokinetics; D005753:Gastric Mucosa / Q000201:enzymology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009962:Orotate Phosphoribosyltransferase / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D013940:Thymidylate Synthase / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D009962:Orotate Phosphoribosyltransferase; D005472:Fluorouracil