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

Clinical application of sensitive gene detection of various drugs in staged ⅢA-N2 NSCLC neoadjuvant chemotherapy

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(b DNA-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m RNA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m RNA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m RNA表达间存在明显的相关性(P<0.05)。ERCC1及TUBB3的m RNA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m RNA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m RNA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m RNA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。

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 m A-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 ERCC 1, BRCA 1,TYMS, RRM 1 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 neoadiuvant chemotherapy.