Association of mutant EGFR L858R and exon 19 concentration in circulating cell-free DNA using droplet digital PCR with response to EGFR-TKIs in NSCLC

  • Authors:
    • Yan‑Juan Zhu
    • Hai‑Bo Zhang
    • Yi‑Hong Liu
    • Ya‑Zhen Zhu
    • Jun Chen
    • Yong Li
    • Jian‑Ping Bai
    • Li‑Rong Liu
    • Yan‑Chun Qu
    • Xin Qu
    • Xian Chen
    • Guang‑Juan Zheng
  • View Affiliations

  • Published online on: June 20, 2017     https://doi.org/10.3892/ol.2017.6425
  • Pages: 2573-2579
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Abstract

The present study aimed to determine the diagnostic concordance of plasma epidermal growth factor receptor (EGFR) mutation using droplet digital polymerase chain reaction (ddPCR) with tumor tissue samples and the predictive clinical significance of plasma EGFR mutation concentration. Plasma DNA samples from patients with non‑small cell lung cancer (NSCLC) were analyzed for EGFR exon 21 codon 858 (L858R) mutation, deletion of exon 19 (ex19del) and exon 20 codon 790 (T790M) mutation using ddPCR. Firstly, the mutations in the plasma samples were compared with the matched tumor samples to determine the concordance. Secondly, image examination follow‑ups were analyzed to assess the association between plasma EGFR mutation concentration and patients' response to EGFR‑tyrosine kinase inhibitors (TKIs). A total of 51 patients with NSCLC were enrolled, including 48 newly diagnosed patients. Compared with tumor tissue samples, the sensitivity and specificity of ddPCR were 76.19% (16/21) and 96.55% (28/29) for mutant L858R, and 88.89% (8/9) and 100% (41/41) for ex19del, respectively. No patient exhibited the T790M mutation in the tumor tissue or plasma samples. Furthermore, 5 patients with the L858R mutation and 4 patients with ex19del in plasma and tumor tissue samples had been followed up with image examination for ≥3 months following EGFR‑TKI treatment. The baseline mutant EGFR concentrations were positively correlated with a reduction in tumor burden (Spearman's r=0.7000, P=0.0358). When analyzed separately, ex19del concentrations (Spearman's r=1.0000, P<0.0001) were also positively correlated with the reduction, while mutant L858R concentrations were not (Spearman's r=0.7000, P=0.1881). In the present study, detection of plasma EGFR mutations using ddPCR exhibited sufficient concordance with tumor tissue sample results. Baseline plasma mutant EGFR and ex19del concentrations were significantly and positively correlated with response to EGFR-TKIs.
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August-2017
Volume 14 Issue 2

Print ISSN: 1792-1074
Online ISSN:1792-1082

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Spandidos Publications style
Zhu YJ, Zhang HB, Liu YH, Zhu YZ, Chen J, Li Y, Bai JP, Liu LR, Qu YC, Qu X, Qu X, et al: Association of mutant EGFR L858R and exon 19 concentration in circulating cell-free DNA using droplet digital PCR with response to EGFR-TKIs in NSCLC. Oncol Lett 14: 2573-2579, 2017
APA
Zhu, Y., Zhang, H., Liu, Y., Zhu, Y., Chen, J., Li, Y. ... Zheng, G. (2017). Association of mutant EGFR L858R and exon 19 concentration in circulating cell-free DNA using droplet digital PCR with response to EGFR-TKIs in NSCLC. Oncology Letters, 14, 2573-2579. https://doi.org/10.3892/ol.2017.6425
MLA
Zhu, Y., Zhang, H., Liu, Y., Zhu, Y., Chen, J., Li, Y., Bai, J., Liu, L., Qu, Y., Qu, X., Chen, X., Zheng, G."Association of mutant EGFR L858R and exon 19 concentration in circulating cell-free DNA using droplet digital PCR with response to EGFR-TKIs in NSCLC". Oncology Letters 14.2 (2017): 2573-2579.
Chicago
Zhu, Y., Zhang, H., Liu, Y., Zhu, Y., Chen, J., Li, Y., Bai, J., Liu, L., Qu, Y., Qu, X., Chen, X., Zheng, G."Association of mutant EGFR L858R and exon 19 concentration in circulating cell-free DNA using droplet digital PCR with response to EGFR-TKIs in NSCLC". Oncology Letters 14, no. 2 (2017): 2573-2579. https://doi.org/10.3892/ol.2017.6425