title: Combination of O6-methylguanine-DNA methyltransferase and thymidylate synthase for the prediction of fluoropyrimidine efficacy.
abstract: We investigated the correlation between the response to fluoropyrimidines as first-line therapy and the expressions of genes in patients with primary colorectal cancer (CRC). The study group comprised 92 patients with metastatic CRC. Total RNA was isolated from laser-captured tumour cells in surgically resected primary lesions, and gene expression was quantitatively evaluated by real-time RT-PCR assay. Low thymidylate synthase (TS), low gamma-glutamyl hydrolase, high reduced folate carrier 1, high O6-methylguanine-DNA methyltransferase (MGMT) and low cyclin E expressions were associated with a good response (P=0.0030, 0.0250, 0.0120, 0.0030 and 0.0020, respectively) on univariate analysis. On multivariate logistic regression analysis, TS and MGMT remained independent predictors of the response. The clinical response rates were 63.2% in the low TS or high MGMT group and 14.3% in high TS and low MGMT group (P<0.0001). The combination of high TS and low MGMT expression is a significant predictor of a poor response to fluoropyrimidine treatment.
authors: Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
authors: Takako Eguchi
authors: TE
authors: Nakajima
authors: Yasuhide
authors: Y
authors: Yamada
authors: Tadakazu
authors: T
authors: Shimoda
authors: Junichi
authors: J
authors: Matsubara
authors: Ken
authors: K
authors: Kato
authors: Tetsuya
authors: T
authors: Hamaguchi
authors: Yasuhiro
authors: Y
authors: Shimada
authors: Yoshihiro
authors: Y
authors: Okayama
authors: Toshinori
authors: T
authors: Oka
authors: Kuniaki
authors: K
authors: Shirao
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000401:mortality; D019175:DNA Methylation; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000235:genetics* / Q000378:metabolism; D011237:Predictive Value of Tests; D012189:Retrospective Studies; D016019:Survival Analysis; D013940:Thymidylate Synthase / Q000378:metabolism*
chemical_list: D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D019853:O(6)-Methylguanine-DNA Methyltransferase