Gene expression of 5-fluorouracil metabolic enzymes in primary gastric cancer: correlation with drug sensitivity against 5-fluorouracil.
Thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), and orotate phosphoribosyltransferase (OPRT) have been reported to be predictive parameters for the efficacy of fluoropyrimidine-based chemotherapy. mRNA expression of TS, DPD, TP, and OPRT were quantified by reverse-transcriptase polymerase chain reaction after harvesting cancer cells from 93 paraffin-embedded specimens of gastric cancer through laser capture microdissection. In vitro chemosensitivity testing by histoculture drug response assay was performed with surgically resected primary lesions of the same 93 patients. No significant correlation was observed between the mRNA expression and location of the tumor, histopathologic type, clinical stage, and other clinicopathologic variables, with the exception that OPRT mRNA had a weak correlation with drug sensitivity against 5FU (R=0.219, p=0.0343). OPRT was considered to have a major impact on drug sensitivity, although not sufficiently so to enable prediction of 5FU sensitivity solely based on the mRNA expression of this enzyme.
Kodera
Yasuhiro
Y
Department of Surgery II, Nagoya University Graduate School of Medicine 65, Tsurumai-cho, Showa-ku, Nagoya, Aichi 466-8550, Japan. ykodera@med.nagoya-u.ac.jp
Ito
Seiji
S
Fujiwara
Michitaka
M
Mochizuki
Yoshinari
Y
Nakayama
Goro
G
Ohashi
Norifumi
N
Koike
Masahiko
M
Yamamura
Yoshitaka
Y
Nakao
Akimasa
A
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D001483:Base Sequence; D004247:DNA; D017931:DNA Primers; D005472:Fluorouracil / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D016612:Paraffin Embedding; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics / Q000473:pathology*
D000964:Antimetabolites, Antineoplastic; D017931:DNA Primers; D012333:RNA, Messenger; D004247:DNA; D005472:Fluorouracil