晚期胃癌患者铂类化疗前后外周血中ERCC1mRNA的表达及其意义

目的研究晚期胃癌患者铂类化疗前后外周血中切除修复交叉互补基因1（excision repair cross-comple-menting 1,ERCC1）mRNA的表达情况,探讨其表达与胃癌患者铂类继发耐药的相关性。方法收集162例经病理学确诊的晚期胃癌患者,通过膜过滤分离外周血循环肿瘤细胞（CTC）,用抗体和核酸染料染色细胞核后进行激光扫描细胞计数仪分析,筛选出DAPI＋CK8＋CD45-CTC阳性的患者,然后采用半定量RT-PCR方法检测此类胃癌患者含铂方案化疗前后其外周血中ERCC1mRNA的表达。同时对完成2个周期化疗后的此类患者按照RECIST标准分为有效组和无效组,比较两组患者化疗前后ERCC1mRNA表达的变化。结果 （1）162例患者中有108例经激光扫描细胞计数仪筛选出DAPI＋CK8＋CD45-CTC,检出率为66.67%。（2）108例患者含铂方案化疗后外周血中ERCC1mRNA表达阳性率为70.30%。（3）108例患者化疗前ERCC1mRNA平均表达水平为（31.71±14.77）%,化疗后升高为（47.45±14.67）%,化疗后显著高于化疗前（P〈0.01）。（4）有效组与无效组化疗前ERCC1mRNA表达水平无明显差异（P〉0.05）,化疗后两组有显著差异（P〈0.01）;有效组化疗前后ERCC1mRNA表达水平无明显差异（P〉0.05）;无效组化疗前后ERCC1mRNA表达水平有显著差异（P〈0.01）。结论膜滤过联合激光扫描细胞计数仪可有效检测晚期胃癌患者外周血中的CTC,且特异性高;含铂方案化疗后晚期胃癌患者外周血中ERCC1mRNA表达水平升高,提示铂类化疗后肿瘤细胞可能产生了继发耐药。

Excision Repair Cross-complementing 1 in Peripheral Blood of Advanced Gastric Cancer Patients Before and After Platinum-based Chemotherapy

Objective To investigate the relationship between the expression of ERCC1 and platinum resistance in peripheral blood of advanced gastric cancer patients before and after platinum-based chemotherapy.Methods One hundred sixty-two with advanced gastric cancer patients confirmed by pathology or cytology were included.The peripheral bloods of every 162 patients before chemotherapy were collected.The cells of DAPI ＋ CK8 ＋ CD45 -were selected.Expression of ERCC1 in their peripheral blood before or after platinum-based chemotherapy was measured by semi-quantitative RT-PCR,and all patients who received 2 cycles could be evaluated.Results（1） The cells were identified as circulating tumor cells if they were DAPI ＋ CK8 ＋ CD45 -cells,108 samples in 162 patients with advanced gastric cancer were detected with the CTCs（P 0.01）.（2） The rate of ERCC1 expression in the peripheral blood of 108 patients was 70.30%.（3） The ERCC1 mRNA levels after chemotherapy（47.45 ± 14.67） % ] were higher than those before （31.71 ± 14.77） % ]（P 0.01）.（4） The difference of ERCC1 expression between the responders and non-responders after chemotherapy were significant（P 0.01）.The difference of ERCC1 expression in the non-responders before and after chemotherapy were significant（P 0.01）.Conclusion The way to detect circulating tumor cells in advanced gastric cancer patients provides a simple and effective method for early diagnosis of cancer;the expression of ERCC1 in peripheral blood of advanced gastric cancer patients suggests that ERCC1 is associated with acquired platinum resis tance.