摘要
目的探讨药物相关分子核苷酸切除修复交叉互补基因1（ERCCl）和DNA拓扑异构酶I（TOPOI）的表达在转移性结直肠癌个体化治疗中的临床价值。方法选取复旦大学附属华东医院普外科2009年6月至2011年12月结直肠癌伴远处转移的手术患者共90例，随机数字表法完全随机分为试验组和对照组，各45例，两组性别、年龄及TNM分期均具有可比性。术后试验组根据检测结果行个体化化疗，对照组随机选择化疗方案。应用免疫组织化学染色对两组患者肿瘤组织中ERCCl和TOPOI的表达进行检测，以Kaplan—Meier方法计算术后累积生存期，Log—Rank检验比较组间差异；X2分析或Fisher’s精确概率分析比较疗效差异。结果试验组与对照组间ERCCl及TOPOI的表达情况差异均无统计学意义（x。=0．46、0．30，均P〉0．05）。试验组中位生存时间281d，受益比51．1％（23／45）；对照组中位生存时间246d，受益比44．4％（20／45）；差异也均无统计学意义（均P〉0．05）。预期药物耐受组（ERCCl高表达或TOPOI低表达）的中位生存时间196d，受益比4／14；预期药物敏感组（ERCCl低表达或TOPOI高表达）的中位生存时间304d，受益比51．3％（39／76）；预期药物敏感组较耐药组中位生存期长，受益比高（均P〈0．05）。结论肠癌组织中药物相关分子的表达与患者的疗效密切相关，ERCCl低表达者使用奥沙利铂或TOPOI高表达者使用伊立替康可延长生存，提高疗效。利用药物相关分子检测来指导用药，对提高转移性结直肠癌患者的疗效有一定的应用价值。
Objective To explore the clinical values of detecting drug related molecules excision repair cross complementing 1 （ ERCC1 ） and top-oisomerase I （ TOPOI ） in individualized therapies of metastatic colorectal cancer. Methods From June 2009 to December 2011, 90 patients at Huadong Hospital with metastatic colorectal cancer were randomly separated into 2 groups after operation. Each group had 45 patients without difference in gender, age or TNM stage. The expressions of ERCC1 and TOPO I in cancer tissues were detected by immunehistochemical staining. The testing group received individualized chemotherapies following the expression results while the control group had random chemotherapies. The survival difference between two groups was analyzed by log-rank test and Kaplan-Meier analysis. And curative effect was analyzed by X2 or Fisher＇s analysis. Results The expressions of ERCC1 and TOPO[ had no statistical significance between two groups （ both P 〉 0. 05 ）. In the testing group, the median survival time was 281 days and the beneficial ratio 51.1% （23/45） versus 246 days and 44.4% （20/45） respectively in the control group. The inter-group comparisons of survival （ P = 0. 235 ） and curative effect （~2 = 0. 04, P 〉 0. 05 ） showed no statistical significance. In the estimated drug tolerated group （ ERCC1 high expression or TOPO 1 low expression）, the median survival time was 196 days and the beneficial ratio 4/14 versus 304 days and 51.3% （39/76） in the estimated drug sensitive group. The inter-group comparisons of survival and curative effect （ both P 〈 0. 05 ） had statistical significance. The median survival time and beneficial ratio significantly increased in estimated drug sensitive group than those in estimated drug tolerated group. Conclusions The expression of drug related molecule in colorectal cancer tissue is significantly associated with curative effect in patients. Patients with down-regulated ERCC1 on Oxaliplatin or up-regulated TOPO I on Irinotecan have lo
出处
《中华医学杂志》
CAS
CSCD
北大核心
2013年第48期3852-3856,共5页
National Medical Journal of China
基金
卫生部科研基金（W2012FZ093）
关键词
结直肠肿瘤
分子诊断技术
个体化医学
ERCC1蛋白
Colorectal neoplasms
Molecular diagnostic techniques
Individualized medicine
ERCC1 protein, human
