RRM1和ERCC1基因外周血中表达水平与吉西他滨联合铂类治疗晚期非小细胞肺癌疗效的相关性研究

RRM1 and ERCC1 expressions and their relationship with gemcitabine and platinum in advanced non-small cell lung cancer

目的:探讨外周血中DNA修复基因RRM1(核苷酸还原酶,ribonucleotide reductase M1)和ERCCl(切除修复交叉互补组基因1,excision repair cross-complementation 1)的表达水平与吉西他滨联合铂类治疗非小细胞肺癌(Nonsmall-cell lung cancer,NSCLC)疗效的相关性。方法:SYBR荧光实时定量PCR检测NSCLC组织和外周血中RRM1和ERCC1mRNA表达水平。分类变量之间进行χ2检验,连续性变量之间进行Spearman等级相关性分析;总体生存率的比较采用Kaplan-Meier生存曲线和log-rank检验。结果:本研究中,34例晚期NSCLC患者外周血RRM1和ERCC1mRNA表达水平进行了有效地检测,22例病例同时进行了肿瘤组织和外周血的基因检测。RRM1mRNA的相对表达量在外周血和肿瘤组织中存在线性相关性(R2=0.045,P=0.048),而ERCC1在两者之间无线性相关(R2=0.016,P=0.251)。RRM1低表达组的生存期(16.0月)明显长于高表达组(12.5月)(Log-rank 3.980,P=0.046)。而ERCC1的表达在两组间无统计学意义(P>0.05)。结论:研究表明,在入组的NSCLC患者中,外周血中RRM1低表达组的生存期明显长于高表达组,对化疗反应的有效率更高,其结果有助于筛选出接受吉西他滨联合铂类化疗方案的患者。

AIM： To evaluate the predictive value of gene expression of ribonucleotide reductase M1（RRM1） and excision repair cross-complementation 1（ERCCl） in peripheral blood from Chinese patients with non-small-cell lung cancer（NSCLC） treated with gemcitabine plus platinum.METHODS： SYBR real-time PCR was used to determine the tumor tissue and peripheral blood RRM1 and ERCC1 mRNA expression levels in NSCLC patients.The χ2 test was used to analyze categorical variables and Spearman rank correlation analysis was used to analyze continuous variables.Kaplan-Meier survival curves and the log-rank test were used for the comparison of overall survival rates.RESULTS：In the present study,34 Chinese patients with histologically confirmed stages IIIB and IV NSCLC were recruited;the tumor tissue and peripheral blood gene expression levels were measured in 22 patients.Linear correlations were observed between peripheral blood and tumor tissue expression levels for RRM1（R2=0.045,P=0.048）,while no correlation was detected for ERCC1（R2=0.016,P=0.251）.Subjects with low peripheral blood RRM1 expression survived longer than those with high RRM1 expression（16.0 vs12.5 months,log-rank 3.980,P=0.046）.The expression of ERCC1 showed no obvious differences between the two groups.CONCLUSION： The study demonstrates increased survival and superior efficacy of gemcitabine and cisplatin combination chemotherapy in the treatment of NSCLC patients with low peripheral blood RRM1 expression.The results contribute to the selection of patients who are most suitable for treatment with gemcitabine and cisplatin combination chemotherapy.