RRM1、β-Tubb3、ERCC1表达在Ⅲb/Ⅳ期非小细胞肺癌个体化治疗中的研究

The significance of the RRM1,β-Tubb3 and ERCC1 expressions in the individual treatment of stage Ⅲb/Ⅳ non-small cell lung cancer

目的:探讨Ⅲb/Ⅳ期非小细胞肺癌(NSCLC)组织中核苷酸还原酶M1(RRM1)、人微管蛋白β3(β-Tubb3)和核苷酸切除修复互补基因1(ERCC1)表达与吉西他滨、紫杉类和铂类药物疗效之间的关系。方法:Ⅲb/Ⅳ期NSCLC患者480例,随机分为试验组和对照组各240例,试验组采用实时荧光定量聚合酶链反应-高分辨溶解曲线法检测石蜡组织标本中RRM1、β-Tubb3、ERCC1 mRNA的表达,并根据RRM1、β-Tubb3表达结果,试验组选择铂类联合吉西他滨(GP方案)、长春瑞滨(NP方案)、紫杉醇(TP方案)或培美曲赛的两药化疗方案;对照组随机给予任何一种两药联合化疗。比较2组化疗疗效及总生存期。结果:试验组和对照组的客观缓解率分别为66.1%和31.7%,疾病控制率分别为79.7%和46.3%,差异均有统计学意义(P<0.01);总生存期分别为11.2个月和9.8个月,差异无统计学意义(P>0.05)。GP方案治疗后试验组患者客观缓解率为70.7%,较对照组32.6%显著增高(P<0.01)。NP、TP方案治疗后试验组患者客观缓解率为66.7%,较对照组29.5%显著增高(P<0.01)。试验组ERCC1低表达与高表达患者客观缓解率分别为78.7%和50.9%,差异有统计学意义(P<0.01),低表达与高表达生存期分别11.4个月和10.9个月,差异无统计学意义(P>0.05)。结论:依据RRM1、β-Tubb3表达水平指导Ⅲb/Ⅳ期NSCLC个体化治疗较随机选用标准一线化疗方案可明显提高客观缓解率。

Objective： To investigate the relationship between the expressions of human tubulin beta-3 Chain （β-Tubb3）, ribonucleotide reductase 1 （ RRM1 ） and excision repair cross compementation 1 （ ERCC1 ） in stage ⅢⅣ/IV non-small cell lung cancer （NSCLC） and treatment effects with gemcitabine, taxanes and platinum. Methods：Four hundred and eighty patients with stage Ⅲb/Ⅳ NSCLC were randomly divided into the test group and control group（240 cases each group）. The mRNA expressions of RRM1, β-Tubb3 and ERCC1 in paraffin-embedded tissue sample from the test group were detected using fluorescence qnantitative-HRM method,the patients from the test group were treated with GP ,NP ,TP or cis-platinum combined with Pemetrexed chemotherapy regimens according to their RRM1 and β-Tubb3 expressions levels, respectively. The control group were treated with a random chemotherapy regimen. The chemotherapeutic effects and overall survival of two groups were observed. Results：The objective response rates in test group and controlgroup were 66.1% and 31.7% ,respectively. The disease control rates in two groups were 79.7% and 46.3% , the difference of which was statistical significance（P 〈0.01 ）. The overall survival in two groups were 11.2 months and 9.8 months, the difference of which had no statistical significance （ P 〉 0.05 ）. The objective response rate in test group treated with GP program（70.7% ） was significantly higher than that in the control group（ 32.6% ） （ P 〈 0.01 ） ,the objective response rate in test group treated with NP and TP program （66.7%） was significantly higher than that in the control group（29.5% ） （ P 〈 0.01 ）. The objective response rates in test group with low and high ERCC1 expressions were78.7% and 50.9%, respectively,the difference of which had statistical significance（P 〈 0.01 ）. The overall survival in test group with low and high ERCC1 expressions were 11.4 months and 10.9 months ,respectively ,the difference of which had no statistical significance （ P 〉 0.05 ）. Conclusions ： The expression levels of RRM 1 and β-Tubb3 in patients with stage Ⅲb/Ⅳ NSCLC can guide the selecting of chemotherapy regimen, which can significantly increase the response rate.