RRM1、-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,-Tubb3 and ERCC1 expressions in the individual treatment of stage Ⅲb/Ⅳ non-small cell lung cancer
-
摘要: 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3(-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、-Tubb3、ERCC1 mRNA的表达,并根据RRM1、-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(P0.01);总生存期分别为11.2个月和9.8个月,差异无统计学意义(P0.05)。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(P0.01)。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(P0.01)。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(P0.01),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(P0.05)。结论:依据RRM1、-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。
-
关键词:
- 癌,非小细胞肺 /
- 人微管蛋白3 /
- 核苷酸还原酶M1 /
- 核苷酸切除修复互补基因1
Abstract: Objective: To investigate the relationship between the expressions of human tubulin beta-3 Chain( -Tubb3), ribonucleotide reductase 1( RRM1) and excision repair cross compementation 1( ERCC1) in stage Ⅲb / 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,-Tubb3 and ERCC1 in paraffin-embedded tissue sample from the test group were detected using fluorescence quantitative-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 -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 control group 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 RRM1 and -Tubb3 in patients with stage Ⅲb/Ⅳ NSCLC can guide the selecting of chemotherapy regimen,which can significantly increase the response rate.-
Key words:
- carcinoma /
- non-small cell lung /
- human tubulin beta-3 chain /
- ribonucleotide reductase 1
-
[1] Schiller JH, Harrington D, Belani CP, et al. Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer[J]. N Engl J Med, 2002, 346(2):92-98. [2] Liu H, Liang Y, Li Y, et al. Gene silencing of BAG-1 modulates apoptotic genes and sensitizes lung cancer cell lines to cisplatin-induced apoptosis[J]. Cancer Biol Ther, 2010, 9(10):832-840. [3] Rosell R, Felip E. Predicting response to paclitaxel/carboplatin-based therapy in non-small cell lung cancer[J]. Semin Oncol, 2001, 28(4 Suppl 14):37-44. [4] Stewart DJ. Mechanisms of resistance to cisplatin and carboplatin[J]. Crit Rev Oncol Hematol, 2007, 63(1):12-31. [5] Danesi R, Pasqualetti G, Giovannetti E, et al. Pharmacogenomics in non-small-cell lung cancer chemotherapy[J]. Adv Drug Deliv Rev, 2009, 61(5):408-417. [6] Toschi L, Cappuzzo F. Impact of biomarkers on non-small cell lung cancer treatment[J]. Target Oncol, 2010, 5(1):5-17. [7] 杨志坚, 刘德森, 陈发龙, 等. 肺癌组织中 RRM1 表达对预测 GP 化疗方案疗效的作用[J]. 中国癌症防治杂志, 2009, 1(2):124-126. [8] Davidson JD, Ma L, Flagella M, et al. An increase in the expression of ribonucleotide reductase large subunit is associated with gemcitabine resistance in non-small cell lung cancer cell lines[J]. Cancer Res, 2004, 64(11):3761-3766. [9] Zhou W, Liu G, Park S, et al. Gene-smoking interaction associations for the ERCC1 polymorphisms in the risk of lung cancer[J]. Cancer Epidemiol Biomarkers Prev, 2005, 14(2):491-496. [10] Zhou W, Gurubhagavatula S, Liu G, et al. Excision repair cross-complementation group 1 polymorphism predicts overall survival in advanced non-small cell lung cancer patients treated with platinum-based chemotherapy [J]. Clin Cancer Res, 2004, 10(15):4939-4943. [11] Yan D, Wei P, An G, et al. Prognostic potential of ERCC1 protein expression and clinicopathologic factors in stage Ⅲ/N2non-small cell lung cancer[J]. J Cardiothorac Surg, 2013, 8 (1):141-149. -
点击查看大图
计量
- 文章访问数: 2672
- HTML全文浏览量: 274
- PDF下载量: 160
- 被引次数: 0
下载:
