EGFR基因CA-SSR多态与晚期非小细胞肺癌吉非替尼临床疗效的关系

Relation between CA-SSR polymorphism of EGFR gene and clinical outcome of patients with advanced non-small cell lung cancer treated with gefitinib

目的研究EGFR基因第1内含子区CA-SSR多态性与晚期非小细胞肺癌患者吉非替尼临床疗效的相关性。方法对80例接受过吉非替尼治疗的晚期非小细胞肺癌患者进行了分析。采用PCR扩增和直接序列测定的方法确定这80例肺癌患者外周血DNA样本中CA-SSR多态的基因型,统计学分析CA-SSR多态性与患者临床疗效的相关性。结果80例患者中共检测到11种不同CA-SSR等位基因型,包含的CA重复序列数为10～24。携带短CA重复序列的患者(至少一条等位基因CA重复数≤16)吉非替尼治疗后的临床获益率为88.0%,而在长CA重复序列的患者(两条等位基因CA重复数均>16)为50.9%,CA-SSR多态性与近期疗效具有显著的相关性(P=0.005),但两组患者的无进展生存和总生存差异均无显著性。结论EGFR基因第1内含子区CA-SSR多态性可以应用于临床预测晚期非小细胞肺癌患者吉非替尼的近期疗效。

Objective To investigate the association of CA-SSR polymorphism in intron 1 of the EGFR gene with clinical outcome in patients with advanced non-small cell lung cancer （ NSCLC ） treated with gefitinib. Methods Eighty patients with advanced NSCLC treated with gefitinib were eligible for analysis. Polymerase chain reaction （PCR） and direct DNA sequencing were used to determine CA-SSR polymorphism in DNA from peripheral blood cells of the NSCLC patients. The correlation of CA-SSR polymorphism with clinical outcomes was analyzed. Results Eleven different CA-SSR alleles were detected in the 80 patients,with the number of CA dinucleotide repeats ranging from 10 to 24. The clinical benefit rate after gefitinib treatment was 88.0% in patients with short CA repeat （ at least one allele CA repeat ≤ 16 ）, and 50.9% in patients with long CA repeat（ CA repeat of both alleles 〉 16）. The CA-SSR polymorphism was significantly correlated with the clinical response to gefitinib （ P = 0.005 ）, while the progression-free survival and overall survival were similar in both groups. Conclusion CA-SSR polymorphism in intron 1 of the EGFR gene may be predictive for clinical response to gefitinib in patients with advanced NSCLC.