Open AccessGene expression in colorectal cancer and in vitro chemosensitivity to 5‐fluorouracil: A study of 88 surgical specimens
Author(s) -
Yoshinare Kentaro,
Kubota Tetsuro,
Watanabe Masahiko,
Wada Norihito,
Nishibori Hideki,
Hasegawa Hirotoshi,
Kitajima Masaki,
Takechi Teiji,
Fukushima Masakazu
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01495.x
Subject(s) - dihydropyrimidine dehydrogenase , thymidine phosphorylase , thymidylate synthase , fluorouracil , colorectal cancer , receiver operating characteristic , microbiology and biotechnology , cancer , medicine , oncology , biology , cancer research
To predict the sensitivity of colorectal cancer to 5‐fluorouracil (5‐FU), we compared the gene expression of surgically obtained colorectal cancer specimens with chemosensitivity to 5‐FU as detected by 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H tetrazolium bromide (MTT) assay. Eighty‐eight patients with advanced and/or metastatic colorectal cancer provided written informed consent and entered the trial from September 2000 to October 2001. Fresh surgical specimens were used for the MTT assay, and sensitivity to 5‐FU was evaluated at a cutoff concentration of 50 μg/ml and 48‐h incubation time. Frozen samples were stored at −80°C until mRNA analysis of thymidylate synthetase (TS), dihydropyri‐midine dehydrogenase (DPD), thymidine phosphorylase (TP), es‐nucleoside transporter (NT), and E2F1 by real‐time RT‐PCR. The correlations between the variables were analyzed, and the predictive value of these mRNAs was assessed statistically using a receiver operating characteristic (ROC) curve. NT and DPD, TP and DPD, and TP and NT mRNA expression levels correlated significantly, while TS and E2F1 showed no correlations. High NT expression was associated with low sensitivity to 5‐FU (P<0.013), as were high DPD and E2F1 expression ( P <0.022 for both). High TP mRNA expression correlated with low sensitivity to 5‐FU ( P <0.034), although high TS mRNA expression did not. ROC curves indicated that DPD and NT mRNAs were possible predictors of sensitivity to 5‐FU, with cutoff values of 0.6 and 0.4, respectively. The sensitivity of colorectal cancer to 5‐FU may be regulated by DPD, the rate‐limiting enzyme of catabolism, and NT, an important transmembrane transporter of nucleosides.