【摘要】 目的:通过血清循环DNA的基因突变检测,筛选EGFR突变型肺癌患者并评估靶向性药物吉非替尼对其的临床疗效。方法:从肺癌患者血清中提取DNA,采用PCR扩增和基因测序检测EGFR突变。结果:116例肺癌血样中检出EGFR突变46例,突变率为39.7%,其中外显子19和21突变分别占65.2%(30/46例)和34.8%(16/46例),EGFR基因突变多见于女性患者和肺腺癌(包括腺鳞癌)患者。对20例肺癌的进一步分析证明,血清EGFR基因突变类型与患者自身肿瘤的突变类型相同。另外通过血清循环DNA基因检测法筛选了19例化疗失败的突变型晚期肺癌进行吉非替尼靶向治疗,客观有效率为52.6%,病情控制率为89.5%,中位无进展生存时间为8个月,中位生存时间为12个月,2年生存率达到33.3%。结论:证实血清循环DNA与肿瘤组织DNA的EGFR基因突变一致;以血清循环EGFR突变检测结果为依据选择分子靶向性药物吉非替尼治疗,对晚期肺癌患者疗效明显。更多还原

【Abstract】 Objective:To detect somatic mutations in epidermal growth factor receptor(EGFR) in the serum circulating DNA,screen the EGFR-mutated lung cancer patients,and evaluate the clinical effects of the genetically targeted drug gefitinib.Methods:DNA was extracted from the serum specimens of patients and amplified by PCR.The EGFR mutations in PCR product were detected by direct sequence analysis.Results:Somatic mutations of EGFR were identified in serum from 46 of the 116 cases(39.7%),including 30 cases(65.2%) in exon 19 and 16 cases(34.8%) in exon 21.Female patients and those patients with adenocarcinoma(including adenosquamous carcinoma) had an increased frequency of mutations.Further analysis on 20 lung cancer patients demonstrated that the EGFR mutation in serum was consistant with that detected in tumor tissues,suggesting that the EGFR mutations in serum originated from the primary tumor.Based on the screening assay,19 patients with EGFR mutations who failed prior chemotherapy were treated with gefitinib.The response rate was 52.6% and the disease-controlling rate was 89.5%.The median progression-free survival time was 8 months,the median overall survival time was 12 months,and 2-year survival rate was 33.3%.Conclusions:The EGFR mutations in serum circulating DNA are consistant with the mutation in lung cancer tissue.Gefitinib treatment has significant effects on the advanced lung cancer based on the screening results of EGFR mutation.更多还原