Extracellular vesicle-based EGFR genotyping in bronchoalveolar lavage fluid from treatment-naive non-small cell lung cancer patients
Extracellular vesicle-based EGFR genotyping in bronchoalveolar lavage fluid from treatment-naive non-small cell lung cancer patients
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DOI：
10.21037/tlcr.2019.12.16
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发表时间：
2019-12-01
影响因子：
4
通讯作者：
Lee, Kye Young
中科院分区：
文献类型：
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作者：
Hur, Jae Young;Lee, Jong Sik;Lee, Kye Young
背景资料：非小细胞肺癌（NSCLC）患者的细胞外囊泡（EV）中含有反映亲代肿瘤细胞突变状态的双链DNA，因此可以将其转化为临床上有用的基于EV的液体活检，使用从肿瘤部位获得的支气管肺泡灌洗液（BALF）进行表皮生长因子受体（EGFR）基因分型。接受初始肺癌检查的患者接受支气管镜检查，并从肿瘤部位获得BALE。在通过超离心从BALF中分离EV后，提取EV衍生的DNA（EV DNA）用于随后通过肽核酸（PNA）介导的实时PCR进行EGFR基因分型。BALF EV为基础的EGFR基因分型的敏感性，特异性和一致率进行了计算比较，组织genotyping.Results：BALF EV为基础的EGFR基因分型的平均敏感性和特异性分别为76%和87%，而敏感性显着增加的阶段进展。特别是在IV期，BALF EV为基础的EGFR分型确定了所有组织证实的EGFR突变病例（n=31），并检测到6个额外的突变病例。一致率在I期为79%，II期为100%，III期为74%，IV期为92%。随着TNM分期的增高，尤其是有转移时，两者的符合率显著增高（P
Background: Extracellular vesicles (EV) have been proven to contain double-stranded DNA reflecting the mutational status of the parental tumor cells in non-small cell lung cancer (NSCLC), which can be translated into clinically useful EV-based liquid biopsy for Epidermal growth factor receptor (EGFR) genotyping using bronchoalveolar lavage fluid (BALF) obtained from tumor site.Methods: Patients subjected for an initial lung cancer work-up underwent bronchoscopy and BALE was obtained from tumor site. After isolating EVs from BALF by ultracentrifugation, EV-derived DNA (EV DNA) was extracted for subsequent EGFR genotyping performed through peptide nucleic acid (PNA)-mediated Real-Time PCR. The sensitivity, specificity, and concordance rate of BALF EV-based EGFR genotyping were calculated in comparison to tissue genotyping.Results: The average sensitivity and specificity of BALF EV-based EGFR genotyping were 76% and 87%, respectively, while the sensitivity significantly increased as the stage progressed. Especially, in stage IV, BALF EV-based EGFR typing identified all tissue-proven EGFR mutant cases (n=31) and detected 6 additional mutant cases. The concordance rate was 79% in stage I, 100% in stage II, 74% in stage III, and 92% in stage IV. As TNM stage advanced, especially in the presence of metastasis, concordance rate significantly increased (P