基于多种药物敏感基因检测在ⅢA-N2期NSCLC新辅助个体化疗中的应用价值

非小细胞肺癌；新辅助化疗；个体化治疗；基因表达；液相芯片

摘要:

目的：本研究拟通过结合目前指导个体化治疗的5个分子生物学指标对接受过新辅助化疗的ⅢA-N2期非小细胞肺癌（non-small-cell lung cancer，NSCLC）患者进行回顾性研究，评估目前NSCLC个体化治疗靶标的价值及临床意义。方法：用分支DNA-液相芯片法（bDNA-LCT）检测30例ⅢA-N2期NSCLC新辅助化疗后手术切除的肿瘤组织标本中ERCC1、BRCA1、TYMS、RRM1、TUBB3基因的mRNA表达情况，对各基因表达情况与患者新辅助化疗疗效间进行分析，探讨多基因表达对新辅助化疗的指导意义。结果：30例肿瘤组织标本中ERCC1、BRCA1、TYMS、RRM1、TUBB3基因mRNA低表达率分别为10.0%、33.3%、46.7%、46.7%、36.7%；中偏低表达率分别为16.7%、20.0%、23.3%、13.3%、16.7%；中表达率分别为40.0%、13.3%、23.3%、30.0%、26.7%；中偏高表达率分别为6.7%、16.7%、0.0%、6.7%、3.3%；高表达率分别为26.7%、16.7%、6.7%、3.3%、16.7%。统计分析显示各基因mRNA表达间存在明显的相关性（P<0.05）。ERCC1及TUBB3的mRNA表达与化疗疗效间有明显的关系（P=0.019，P=0.001）；在24例行抗微管类/铂类新辅助化疗的患者中，RRM1及TUBB3的mRNA表达与化疗疗效间有明显的关系（P=0.039，P=0.000）。结论：NSCLC中多基因mRNA表达间存在明显的相关性；对IIIA-N2期NSCLC患者行新辅助化疗前所获取的肿瘤组织标本进行个体化基因mRNA表达检测，筛选出合理指标所指导的化疗方案，可以提高新辅助化疗疗效。

Abstract:

Objective：To discuss the efforts towards personalizing delivery of care based on the mRNA expression levels of ERCC1，BRCA1，TYMS，RRM1 and TUBB3 by choosing neoadjuvant chemotherapy for 30 ⅢA-N2 non-small-cell lung cancer（NSCLC） pa－tients. Methods：Postoperative samples from 30 ⅢA-N2 NSCLC patients treated with neoadjuvant chemotherapy were analyzed. mRNA expressions of ERCC1，BRCA1，TYMS，RRM1 and TUBB3 were detected by using branched DNA-liquidchip technology（bDNA-LCT）. Results：The total expressions of 5 genotypes from low to high were detected. Correlations were observed between most of these gene expression levels（P<0.05）. All patients were treated with platinum-based neoadjuvant chemo-therapy. ERCC1 and TUBB3 mRNA expressions were associated with the efficacy of neoadjuvant chemotherapy（P<0.05）；lower expression can predict better response. Among these 24 patients treated with antimicrotubules/platinum based chemotherapy，the mRNA expression levels of RRM1 and TUBB3 could be used to predict the treatment outcomes of chemotherapy（P<0.05）. Conclusion：A clear correlation exists between many genes mRNA expression in NSCLC. The mRNA expression levels of many genes could be detected as predictors of the response to neoadjuvant chemotherapy.