Expression level of thymidylate synthase is a good predictor of chemosensitivity to 5-fluorouracil in colorectal cancer.
BACKGROUND
It is important to seek the appropriate chemotherapy drugs to effectively eliminate colorectal cancers. To avoid unnecessary medication and uncomfortable side effects, it is important to estimate the chemosensitivity of cancers to 5-fluorouracil (5-FU) before chemotherapy.


METHODS
We examined thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD) gene expressions in 23 colorectal cancers, using quantitative reverse transcription-polymerase chain reaction (RT-PCR). We then evaluated the relationship between TS and DPD gene expression levels and the sensitivity of colorectal cancers to 5-FU, as determined by histoculture drug response assay (HDRA).


RESULTS
A significant increase in the TS expression score was observed in 5-FU-sensitive colorectal cancers (0.57 +/- 0.19) compared to 5-FU-resistant ones (1.16 +/- 0.98; P = 0.029), whereas no significant differences in DPD expression scores were observed in 5-FU-sensitive colorectal cancers (0.86 +/- 1.19) compared to 5-FU-resistant ones (0.56 +/- 1.05; P = 0.603).


CONCLUSIONS
TS mRNA may be useful as a predictor of the 5-FU chemosensitivity of colorectal cancers.
Inoue
Tamotsu
T
Gastroenterological Surgery, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8560, Japan.
Hibi
Kenji
K
Nakayama
Goro
G
Komatsu
Yoshinao
Y
Fukuoka
Tomoki
T
Kodera
Yasuhiro
Y
Ito
Katsuki
K
Akiyama
Seiji
S
Nakao
Akimasa
A
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D042943:Dihydrouracil Dehydrogenase (NADP); D004354:Drug Screening Assays, Antitumor; D005472:Fluorouracil / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013940:Thymidylate Synthase / Q000378:metabolism*
D000964:Antimetabolites, Antineoplastic; D042943:Dihydrouracil Dehydrogenase (NADP); D013940:Thymidylate Synthase; D005472:Fluorouracil