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Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients
BACKGROUND/OBJECTIVE: The third-generation epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitor (TKIs), such as osimertinib, designed for targeting the acquired drug-resistant mutation of EGFR T790M, was approved as the first-line therapy for advanced EGFR-mutated non-small cell lung c...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909534/ https://www.ncbi.nlm.nih.gov/pubmed/36776375 http://dx.doi.org/10.3389/fonc.2022.942123 |
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author | Zhang, Hui Hu, Yi Wang, Yan Song, Xia Hu, Ying Ma, Li Yang, Xinjie Li, Kun Qin, Na Wang, Jinghui Lv, Jialin Li, Xi Zhang, Xinyong Zhang, Quan Wu, Yuhua Yao, Guangyin Zhang, Shucai |
author_facet | Zhang, Hui Hu, Yi Wang, Yan Song, Xia Hu, Ying Ma, Li Yang, Xinjie Li, Kun Qin, Na Wang, Jinghui Lv, Jialin Li, Xi Zhang, Xinyong Zhang, Quan Wu, Yuhua Yao, Guangyin Zhang, Shucai |
author_sort | Zhang, Hui |
collection | PubMed |
description | BACKGROUND/OBJECTIVE: The third-generation epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitor (TKIs), such as osimertinib, designed for targeting the acquired drug-resistant mutation of EGFR T790M, was approved as the first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Thus, detection of the EGFR T790M mutation for NSCLC is crucial. However, tissue samples are often difficult to obtain, especially in patients at advanced stages. This study assessed the performances of droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS) in detecting EGFR T790M status and abundance in the plasma ctDNA samples of patients with NSCLC. We also explored the association between T790M status and abundance and the response to third-generation EGFR-TKIs. METHODS: A total of 201 plasma samples with matched tissues, 821 plasma samples, and 56 patients who received third-generation EGFR-TKIs with response evaluation were included in this study. ddPCR and NGS were used to detect the mutation status and abundance of T790M in the tissues and/or blood samples. RESULTS: The results showed that the sensitivity and the specificity of EGFR T790M mutation status detected by ddPCR in plasma samples were 81.82% and 91.85%, respectively, compared with the tissue samples, with a consistency coefficient of 0.740. Among the 821 plasma samples, the positive rates of EGFR T790M detected by ddPCR and NGS were 34.2% (281/821) and 22.5% (185/821), respectively. With NGS results as the reference, the sensitivity and the specificity of ddPCR were 100% and 84.91%, respectively, and the consistency coefficient of the two methods was 0.717. In addition, we found that a higher EGFR T790M abundance was linked to a higher treatment response rate to the third-generation EGFR-TKIs regardless of the classification of the median value of 0.43% (P = 0.016) or average value of 3.16% (P = 0.010). CONCLUSION: Taking these data together, this study reveals that ddPCR is an alternatively potent method for the detection of EGFR T790M in the plasma samples of NSCLC patients. |
format | Online Article Text |
id | pubmed-9909534 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-99095342023-02-10 Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients Zhang, Hui Hu, Yi Wang, Yan Song, Xia Hu, Ying Ma, Li Yang, Xinjie Li, Kun Qin, Na Wang, Jinghui Lv, Jialin Li, Xi Zhang, Xinyong Zhang, Quan Wu, Yuhua Yao, Guangyin Zhang, Shucai Front Oncol Oncology BACKGROUND/OBJECTIVE: The third-generation epidermal growth factor receptor (EGFR) -tyrosine kinase inhibitor (TKIs), such as osimertinib, designed for targeting the acquired drug-resistant mutation of EGFR T790M, was approved as the first-line therapy for advanced EGFR-mutated non-small cell lung cancer (NSCLC). Thus, detection of the EGFR T790M mutation for NSCLC is crucial. However, tissue samples are often difficult to obtain, especially in patients at advanced stages. This study assessed the performances of droplet digital polymerase chain reaction (ddPCR) and next-generation sequencing (NGS) in detecting EGFR T790M status and abundance in the plasma ctDNA samples of patients with NSCLC. We also explored the association between T790M status and abundance and the response to third-generation EGFR-TKIs. METHODS: A total of 201 plasma samples with matched tissues, 821 plasma samples, and 56 patients who received third-generation EGFR-TKIs with response evaluation were included in this study. ddPCR and NGS were used to detect the mutation status and abundance of T790M in the tissues and/or blood samples. RESULTS: The results showed that the sensitivity and the specificity of EGFR T790M mutation status detected by ddPCR in plasma samples were 81.82% and 91.85%, respectively, compared with the tissue samples, with a consistency coefficient of 0.740. Among the 821 plasma samples, the positive rates of EGFR T790M detected by ddPCR and NGS were 34.2% (281/821) and 22.5% (185/821), respectively. With NGS results as the reference, the sensitivity and the specificity of ddPCR were 100% and 84.91%, respectively, and the consistency coefficient of the two methods was 0.717. In addition, we found that a higher EGFR T790M abundance was linked to a higher treatment response rate to the third-generation EGFR-TKIs regardless of the classification of the median value of 0.43% (P = 0.016) or average value of 3.16% (P = 0.010). CONCLUSION: Taking these data together, this study reveals that ddPCR is an alternatively potent method for the detection of EGFR T790M in the plasma samples of NSCLC patients. Frontiers Media S.A. 2023-01-26 /pmc/articles/PMC9909534/ /pubmed/36776375 http://dx.doi.org/10.3389/fonc.2022.942123 Text en Copyright © 2023 Zhang, Hu, Wang, Song, Hu, Ma, Yang, Li, Qin, Wang, Lv, Li, Zhang, Zhang, Wu, Yao and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Oncology Zhang, Hui Hu, Yi Wang, Yan Song, Xia Hu, Ying Ma, Li Yang, Xinjie Li, Kun Qin, Na Wang, Jinghui Lv, Jialin Li, Xi Zhang, Xinyong Zhang, Quan Wu, Yuhua Yao, Guangyin Zhang, Shucai Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients |
title | Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients |
title_full | Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients |
title_fullStr | Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients |
title_full_unstemmed | Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients |
title_short | Application of ddPCR in detection of the status and abundance of EGFR T790M mutation in the plasma samples of non-small cell lung cancer patients |
title_sort | application of ddpcr in detection of the status and abundance of egfr t790m mutation in the plasma samples of non-small cell lung cancer patients |
topic | Oncology |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9909534/ https://www.ncbi.nlm.nih.gov/pubmed/36776375 http://dx.doi.org/10.3389/fonc.2022.942123 |
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