Gene expression in colorectal cancer and in vitro chemosensitivity to 5-fluorouracil:: A study of 88 surgical specimens

Gene expression in colorectal cancer and in vitro chemosensitivity to 5-fluorouracil:: A study of 88 surgical specimens
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DOI:
10.1111/j.1349-7006.2003.tb01495.x
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发表时间:
2003-07-01
期刊:
影响因子:
5.7
通讯作者:
Fukushima, M
Fukushima, M
中科院分区:
医学2区
文献类型:
--
作者:
Yoshinare, K;Kubota, T;Fukushima, M

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为了预测结直肠癌对5-氟尿嘧啶(5-FU)的敏感性,我们比较了手术获得的结直肠癌标本的基因表达与用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基-2H溴化四氮唑(MTT)法检测的5-FU化疗敏感性。2000年9月至2001年10月,88例晚期和/或转移性结直肠癌患者提供了书面知情同意书并进入试验。新鲜手术标本用于MTT试验,并在50 μ g/ml的截止浓度和48小时的孵育时间下评价对5-FU的敏感性。将冷冻样品储存在-80 ℃下,直至通过实时RT-PCR分析胸苷酸合成酶(TS)、二氢嘧啶脱氢酶(DPD)、胸苷磷酸化酶(TP)、esnucleotide转运蛋白(NT)和E2 F1的mRNA。分析变量之间的相关性,并使用受试者工作特征(ROC)曲线统计评估这些mRNA的预测值。NT与DPD、TP与DPD、TP与NT mRNA表达水平显著相关,TS与E2 F1无相关性。NT高表达与5-FU敏感性低有关(P
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 mug/ml and 48-h incubation time. Frozen samples were stored at -80degreesC until mRNA analysis of thymidylate synthetase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine phosphorylase (TP), esnucleoside 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