Combination of p53 codon 72 polymorphism and inactive p53 mutation predicts chemosensitivity to 5-fluorouracil in colorectal cancer
Combination of p53 codon 72 polymorphism and inactive p53 mutation predicts chemosensitivity to 5-fluorouracil in colorectal cancer
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DOI：
10.1002/ijc.24929
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发表时间：
2010-04-01
影响因子：
6.4
通讯作者：
Yamaue, Hiroki
中科院分区：
文献类型：
--
作者：
Tominaga, Toshiji;Iwahashi, Makoto;Yamaue, Hiroki
越来越多的报道显示P53基因多态状态在化疗反应中的临床意义。我们研究了P53基因多态性和突变与结直肠癌患者对5-氟尿嘧啶(5-FU)体外敏感性的关系。用胶原胶微滴包埋培养药敏试验评价5-FU的药敏作用。精氨酸/精氨酸(Arg/Arg)突变无P53突变的肿瘤细胞对5-FU的敏感性显著高于有或无P53突变的肿瘤细胞(p=0.022)，而无P53突变的肿瘤细胞对5-FU的敏感性明显低于有或无P53突变的肿瘤细胞(p=0.002)。在Arg/Arg变异体中，5-FU诱导的非活动性p53突变患者的细胞凋亡率明显高于非活动性P53突变患者(p=0.037)。5-FU治疗后肿瘤组织中Bax和Bcl2蛋白的表达与5-FU敏感性和细胞凋亡率有关。我们的数据显示，无非活动性p53突变的Arg/Arg基因型可预示较好的疗效，而含非活动性p53突变的Arg/Arg基因型对5-FU化疗的疗效较差。P53基因第72位密码子多态性和P53突变状态相结合是结直肠癌对5-FU敏感性的潜在预测指标。
There are increasing reports showing the clinical significance of the p53 polymorphism status in terms of the response to chemotherapy. We investigated whether p53 polymorphism and mutation were associated with in vitro sensitivity to 5-fluorouracil (5-FU) in patients with colorectal cancer. Chemosensitivity to 5-FU was evaluated by the collagen gel droplet embedded culture drug sensitivity test. 5-FU sensitivity of tumor cells without inactive p53 mutation in the arginine/arginine (Arg/Arg) variant was significantly higher than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.022), whereas the 5-FU sensitivity of tumor cells with inactive p53 mutation in the Arg/Arg variant was significantly lower than that of tumor cells with or without inactive p53 mutation in other variants (p = 0.002). In the Arg/Arg variant, apoptotic cells induced by 5-FU treatment in patients without inactive p53 mutation were more markedly increased than those in patients with inactive p53 mutation (p = 0.037). Bax and Bcl-2 protein expressions in tumor tissue treated with 5-FU were associated with both 5-FU sensitivity and the apoptotic cell count. Our data show that the Arg/Arg genotype without inactive p53 mutation could be predictive of a more favorable response and the Arg/Arg genotype with inactive p53 mutation a less favorable response to chemotherapy using 5-FU in CRC. The combination of the p53 codon 72 polymorphism and p53 mutation status is a potential predictive marker of sensitivity to 5-FU in CRC.