RRM1和BRCA1的表达与吉西他滨联合铂类治疗晚期非小细胞肺癌的临床研究

Effect of RRM1 and BRCA1 Expressions on Efficiency of Gemcitabine and Platinum in Patients with Advanced Non-Small Cell Lung Cancer

目的探讨核苷酸还原酶(ribonucleotide reductase M1,RRM1)和乳腺癌易感基因(breast cancer susceptibility gene 1,BRCA1)在外周血中表达及与吉西他滨联合铂类治疗非小细胞肺癌(non-small-cell lung cancer,NSCLC)疗效的关系。方法通过荧光实时定量PCR检测34例NSCLC肺癌患者外周血中RRM1和BRCA1 mRNA表达水平,并与患者的组织病理学类型、临床分期及吉西他滨联合铂类化疗方案疗效的关系进行分析。统计采用线性相关性分析及χ2检验,总体生存率的比较采用Kaplan-Meier生存曲线和Log-rank检验法分析。结果在外周血中RRM1和BRCA1 mRNA表达水平之间无线性相关(P=0.19);RRM1和BRCA1在不同的临床分期(ⅢB和Ⅳ)和组织病理学类型(鳞癌、腺癌)中表达均无差异;在肿瘤化疗反应中,RRM1低表达组有效率(52.9%)高于高表达组(5.9%),差异有显著的统计学意义(P=0.007)。而BRCA1的表达在两组间无统计学意义(P=0.259);RRM1低表达组的生存期(15.5月)明显长于高表达组(11.8月)(P=0.045),而BRCA1的表达水平对生存期无统计学意义(P>0.05)。结论 NSCLC中,RRM1的低表达对化疗反应的有效率更高,生存期更长,有助于选择患者接受吉西他滨联合铂类的一线方案的辅助化疗。

OBJECTIVE To investigate expressions of ribonucleotide reductase M1（RRM1） and breast cancer susceptibility gene 1（BRCA1） in peripheral blood and their relationship with gemcitabine and platinum in advanced non-small cell lung cancer（NSCLC）.METHODS The expression levels of RRM1 and BRCA1 were detected by real-time PCR method in peripheral blood of 34 NSCLC patients.The relationships between the expression and histopathological type,clinical stage,and gemcitabine plus platinum chemotherapy efficacy of NSCLC patients were analyzed by rank correlation and χ2 test.Kaplan-Meier survival curve and Log-rank test.RESULTS The expression level of RRM1 was not significantly correlated with BRCA1（P= 0.19）.Both of RRM1 and BRCA1 had no significance between clinical stage ⅢB and Ⅳ,and between Squamous cell carcinoma and Adenocarcinoma.While,efficiencies in patients with low RRM1 expression level were 52.9%（9/17） and 5.9%（1/17） in patients with high RRM1 expression level（P=0.007）.The survival time were 15.5 months vs 11.8 months respectively.which suggested survival time of patients with low RRM1 expression levels was significantly longer than that of patients with high RRM1 expression levels（P=0.045）.CONCLUSION The patients with low RRM1 expression level had a higher response and longer survival time after the treatment with gemcitabine and platinum.The results may be useful for selecting patients with advanced non-small cell lung cancer with low RRM1 expression levels to accept the chemotherapy with gemcitabine and platinum.