Combination of O6-methylguanine-DNA methyltransferase and thymidylate synthase for the prediction of fluoropyrimidine efficacy.
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.
Nakajima
Takako Eguchi
TE
Gastrointestinal Oncology Division, National Cancer Center Hospital, Tokyo, Japan.
Yamada
Yasuhide
Y
Shimoda
Tadakazu
T
Matsubara
Junichi
J
Kato
Ken
K
Hamaguchi
Tetsuya
T
Shimada
Yasuhiro
Y
Okayama
Yoshihiro
Y
Oka
Toshinori
T
Shirao
Kuniaki
K
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*
D014408:Biomarkers, Tumor; D013940:Thymidylate Synthase; D019853:O(6)-Methylguanine-DNA Methyltransferase