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目的吉西他滨联合顺铂是治疗晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的一线化疗方案,但其有效率仅20%~40%,其较低的化疗有效率与肿瘤耐药相关。研究NSCLC组织中切除修复交叉互补基因1(exeision repair cross-compietionl1,ERCC1)和乳腺癌易感基因1(breast cancer susceptibility gene-1,BRCA1)mRNA的表达及其与铂类化疗敏感性的关系。方法应用实时荧光定量PCR技术检测2009-03-01-2011-04-16武汉钢铁(集团)公司第二职工医院收集的98例晚期NSCLC患者中ERCC1和BRCA1mRNA的表达情况,分析其与含铂联合治疗方案化疗耐药性的关系。结果检测98例患者中ERCC1和BRCA1mRNA的相对表达量,其中位数分别为0.048和0.011,四分位间距IQR分别为0.0058和0.001。ERCC1mRNA的高表达率为56.1%(55/98),其表达在不同性别、年龄、组织学类型及临床分期中差异无统计学意义,P>0.05;BRCA1mRNA的高表达率为64.3%(63/98),其表达在不同性别、年龄、组织学类型及临床分期中差异无统计学意义,P>0.05。在ERCC1mRNA低表达组GP方案化疗客观缓解率为48.8%(21/43),而在高表达组化疗客观缓解率为29.1%(16/55),两组之间比较差异有统计学意义,χ~2=4.0,P=0.045;在BRCA1mRNA低表达组GP化疗客观缓解率为57.1%(20/35),在高表达组GP化疗客观缓解率为28.6%(18/63),差异有统计学意义,χ~2=7.74,P=0.005;ERCC1和BRCA1 mRNA联合低表达组中GP化疗客观缓解率为70.4%(19/27),而其联合高表达组GP化疗客观缓解率仅为21.1%(8/38)。结论 ERCC1、BRCA1mRNA高表达患者在使用含铂化疗方案时疗效差,提示ERCC1和BRCA1 mRNA高表达NSCLC患者对铂类具有耐药性。ERCC1和BRCA1mRNA联合低表达患者在使用含铂方案化疗时有效率更高,提示应用ERCC1和BRCA1mRNA联合检测时,患者可获得更大的益处。
Objective Gemcitabine combined with cisplatin is a first-line chemotherapy for advanced non-small cell lung cancer (NSCLC), but its effective rate is only 20% -40%. The lower effective rate of chemotherapy is related to drug resistance . To investigate the expression of ERCC1 and BRCA1 mRNA in NSCLC tissues and its relationship with the sensitivity of platinum chemotherapy. METHODS: Real-time fluorescence quantitative PCR was used to detect the expression of ERCC1 and BRCA1 mRNA in 98 patients with advanced NSCLC collected from Second Workers’ Hospital of Wuhan Iron and Steel (Group) Corporation. Relationship between chemotherapy regimens and chemotherapy resistance. Results The relative expression levels of ERCC1 and BRCA1 mRNA in 98 patients were detected, with median of 0.048 and 0.011, respectively, and interquartile range of IQR of 0.0058 and 0.001, respectively. The high expression rate of ERCC1 mRNA was 56.1% (55/98). There was no significant difference in the expression of ERCC1 mRNA between different sex, age, histological type and clinical stage (P> 0.05). The high expression rate of BRCA1 mRNA was 64.3% 98). There was no significant difference in the expression between different sex, age, histological type and clinical stage (P> 0.05). The objective response rate was 48.8% (21/43) in GP regimen with low expression of ERCC1 mRNA and 29.1% (16/55) in high expression group, the difference was statistically significant between the two groups, χ ~ 2 = 4.0, P = 0.045. The objective response rate of GP chemotherapy in low BRCA1 mRNA expression group was 57.1% (20/35), and the objective response rate of GP chemotherapy in high expression group was 28.6% (18/63) The objective response rate of GP chemotherapy in combination with ERCC1 and BRCA1 mRNA was 70.4% (19/27), while the combined response rate of GP and ERCC1 combined with high expression group was only 21.1% (χ ~ 2 = 7.74, P = 0.005) (8/38). Conclusions Patients with high expression of ERCC1 and BRCA1 mRNA have poor curative effect when using platinum-containing chemotherapy regimen, suggesting that patients with high expression of ERCC1 and BRCA1 mRNA are resistant to platinum. ERCC1 and BRCA1mRNA combined with low expression of patients with platinum-based chemotherapy is more efficient, suggesting that the combination of ERCC1 and BRCA1mRNA detection, patients can get greater benefits.