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Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients

Mutations in the epidermal growth factor receptor (EGFR) are associated with various solid tumors. This study aimed to compare two methods for the detection of EGFR mutations in circulating tumor DNA (ctDNA) from lung adenocarcinoma (LUAD) patients and to evaluate the clinical significance of EGFR m...

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Autores principales: Hung, Ming-Szu, Lung, Jr-Hau, Lin, Yu-Ching, Fang, Yu-Hung, Huang, Shu-Yi, Jiang, Yuan-Yuan, Hsieh, Meng-Jer, Tsai, Ying-Huang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627967/
https://www.ncbi.nlm.nih.gov/pubmed/31185703
http://dx.doi.org/10.3390/cancers11060803
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author Hung, Ming-Szu
Lung, Jr-Hau
Lin, Yu-Ching
Fang, Yu-Hung
Huang, Shu-Yi
Jiang, Yuan-Yuan
Hsieh, Meng-Jer
Tsai, Ying-Huang
author_facet Hung, Ming-Szu
Lung, Jr-Hau
Lin, Yu-Ching
Fang, Yu-Hung
Huang, Shu-Yi
Jiang, Yuan-Yuan
Hsieh, Meng-Jer
Tsai, Ying-Huang
author_sort Hung, Ming-Szu
collection PubMed
description Mutations in the epidermal growth factor receptor (EGFR) are associated with various solid tumors. This study aimed to compare two methods for the detection of EGFR mutations in circulating tumor DNA (ctDNA) from lung adenocarcinoma (LUAD) patients and to evaluate the clinical significance of EGFR mutations in ctDNA. In this prospective cohort study, the EGFR mutation status of 77 patients with stage IIIB or IV LUAD was first determined using lung cancer tissue. The amplification refractory mutation system (ARMS) and single allele base extension reaction combined with mass spectroscopy (SABER/MassARRAY) methods were also used to detect EGFR mutations in plasma ctDNA from these patients and then compared using the EGFR mutation status in lung cancer tissue as a standard. Furthermore, the relationship between the presence of EGFR mutations in ctDNA after receiving first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy and survival was evaluated. The overall sensitivity and specificity for the detection of EGFR mutations in plasma ctDNA by ARMS and SABER/MassARRAY were 49.1% vs. 56% and 90% vs. 95%, respectively. The agreement level between these methods was very high, with a kappa-value of 0.88 (95% CI 0.77–0.99). Moreover, 43 of the patients who carried EGFR mutations also received first-line EGFR-TKI therapy. Notably, patients with EGFR mutations in plasma ctDNA had significantly shorter progression-free survival (9.0 months, 95% CI 7.0–11.8, vs. 15.0 months, 95% CI 11.7–28.2; p = 0.02) and overall survival (30.6 months, 95% CI 12.4–37.2, vs. 55.6 months, 95% CI 25.8–61.8; p = 0.03) compared to those without detectable EGFR mutations. The detection of EGFR mutations in plasma ctDNA is a promising, minimally invasive, and reliable alternative to tumor biopsy, and the presence of EGFR mutations in plasma ctDNA after first-line EGFR-TKI therapy is associated with poor prognosis.
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spelling pubmed-66279672019-07-23 Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients Hung, Ming-Szu Lung, Jr-Hau Lin, Yu-Ching Fang, Yu-Hung Huang, Shu-Yi Jiang, Yuan-Yuan Hsieh, Meng-Jer Tsai, Ying-Huang Cancers (Basel) Article Mutations in the epidermal growth factor receptor (EGFR) are associated with various solid tumors. This study aimed to compare two methods for the detection of EGFR mutations in circulating tumor DNA (ctDNA) from lung adenocarcinoma (LUAD) patients and to evaluate the clinical significance of EGFR mutations in ctDNA. In this prospective cohort study, the EGFR mutation status of 77 patients with stage IIIB or IV LUAD was first determined using lung cancer tissue. The amplification refractory mutation system (ARMS) and single allele base extension reaction combined with mass spectroscopy (SABER/MassARRAY) methods were also used to detect EGFR mutations in plasma ctDNA from these patients and then compared using the EGFR mutation status in lung cancer tissue as a standard. Furthermore, the relationship between the presence of EGFR mutations in ctDNA after receiving first-line EGFR-tyrosine kinase inhibitor (EGFR-TKI) therapy and survival was evaluated. The overall sensitivity and specificity for the detection of EGFR mutations in plasma ctDNA by ARMS and SABER/MassARRAY were 49.1% vs. 56% and 90% vs. 95%, respectively. The agreement level between these methods was very high, with a kappa-value of 0.88 (95% CI 0.77–0.99). Moreover, 43 of the patients who carried EGFR mutations also received first-line EGFR-TKI therapy. Notably, patients with EGFR mutations in plasma ctDNA had significantly shorter progression-free survival (9.0 months, 95% CI 7.0–11.8, vs. 15.0 months, 95% CI 11.7–28.2; p = 0.02) and overall survival (30.6 months, 95% CI 12.4–37.2, vs. 55.6 months, 95% CI 25.8–61.8; p = 0.03) compared to those without detectable EGFR mutations. The detection of EGFR mutations in plasma ctDNA is a promising, minimally invasive, and reliable alternative to tumor biopsy, and the presence of EGFR mutations in plasma ctDNA after first-line EGFR-TKI therapy is associated with poor prognosis. MDPI 2019-06-10 /pmc/articles/PMC6627967/ /pubmed/31185703 http://dx.doi.org/10.3390/cancers11060803 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Hung, Ming-Szu
Lung, Jr-Hau
Lin, Yu-Ching
Fang, Yu-Hung
Huang, Shu-Yi
Jiang, Yuan-Yuan
Hsieh, Meng-Jer
Tsai, Ying-Huang
Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients
title Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients
title_full Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients
title_fullStr Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients
title_full_unstemmed Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients
title_short Comparative Analysis of Two Methods for the Detection of EGFR Mutations in Plasma Circulating Tumor DNA from Lung Adenocarcinoma Patients
title_sort comparative analysis of two methods for the detection of egfr mutations in plasma circulating tumor dna from lung adenocarcinoma patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6627967/
https://www.ncbi.nlm.nih.gov/pubmed/31185703
http://dx.doi.org/10.3390/cancers11060803
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