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Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients

Mutations identified in the epidermal growth factor receptor (EGFR) predict sensitivity to EGFR-targeted therapy for non-small cell lung carcinoma (NSCLC). We previously reported that Electric Field-Induced Release and Measurement (EFIRM)-based liquid biopsy could detect EGFR ctDNA with >94% conc...

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Autores principales: Li, Feng, Wei, Fang, Huang, Wei-Lun, Lin, Chien-Chung, Li, Liang, Shen, Macy M., Yan, Qingxiang, Liao, Wei, Chia, David, Tu, Michael, Tang, Jason H., Feng, Ziding, Kim, Yong, Su, Wu-Chou, Wong, David T. W.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464208/
https://www.ncbi.nlm.nih.gov/pubmed/32722209
http://dx.doi.org/10.3390/cancers12082041
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author Li, Feng
Wei, Fang
Huang, Wei-Lun
Lin, Chien-Chung
Li, Liang
Shen, Macy M.
Yan, Qingxiang
Liao, Wei
Chia, David
Tu, Michael
Tang, Jason H.
Feng, Ziding
Kim, Yong
Su, Wu-Chou
Wong, David T. W.
author_facet Li, Feng
Wei, Fang
Huang, Wei-Lun
Lin, Chien-Chung
Li, Liang
Shen, Macy M.
Yan, Qingxiang
Liao, Wei
Chia, David
Tu, Michael
Tang, Jason H.
Feng, Ziding
Kim, Yong
Su, Wu-Chou
Wong, David T. W.
author_sort Li, Feng
collection PubMed
description Mutations identified in the epidermal growth factor receptor (EGFR) predict sensitivity to EGFR-targeted therapy for non-small cell lung carcinoma (NSCLC). We previously reported that Electric Field-Induced Release and Measurement (EFIRM)-based liquid biopsy could detect EGFR ctDNA with >94% concordance with tissue-based genotyping. A side-by-side comparison of concordance of EFIRM and droplet digital PCR (ddPCR) for the detection of the two front-line actionable EFGR mutations was performed with paired plasma and saliva samples from 13 NSCLC patients. Deep sequencing analysis based on single-strand DNA library preparation was employed to determine the size distributions of EGFR L858R ctDNA in plasma and saliva samples. EFIRM detected both EGFR mutations with 100% sensitivity in both plasma and saliva samples, whereas ddPCR detected EGFR mutations with sensitivities of 84.6% and 15.4%, respectively. In saliva samples, the majority of EGFR L858R ctDNA fragments detected were <80 bp. Deep sequencing analysis of ctDNA enriched for the EGFR L858R mutation revealed the significant presence of EGFR L858R ctDNA as ultra-short circulating tumor DNA (usctDNA) with the size of 40–60 bp in patient plasma and saliva. Most of usctDNAs are not amplifiable with the current ddPCR assay. Further examination using cell lines and patient biofluids revealed that the majority of usctDNAs were predominately localized in the exosomal fraction. Our study revealed the abundant existence of EGFR ctDNA in the plasma and saliva of NSCLC patients is usctDNA. usctDNA is a novel type of targets for liquid biopsy that can be efficiently detected by EFIRM technology.
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spelling pubmed-74642082020-09-04 Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients Li, Feng Wei, Fang Huang, Wei-Lun Lin, Chien-Chung Li, Liang Shen, Macy M. Yan, Qingxiang Liao, Wei Chia, David Tu, Michael Tang, Jason H. Feng, Ziding Kim, Yong Su, Wu-Chou Wong, David T. W. Cancers (Basel) Article Mutations identified in the epidermal growth factor receptor (EGFR) predict sensitivity to EGFR-targeted therapy for non-small cell lung carcinoma (NSCLC). We previously reported that Electric Field-Induced Release and Measurement (EFIRM)-based liquid biopsy could detect EGFR ctDNA with >94% concordance with tissue-based genotyping. A side-by-side comparison of concordance of EFIRM and droplet digital PCR (ddPCR) for the detection of the two front-line actionable EFGR mutations was performed with paired plasma and saliva samples from 13 NSCLC patients. Deep sequencing analysis based on single-strand DNA library preparation was employed to determine the size distributions of EGFR L858R ctDNA in plasma and saliva samples. EFIRM detected both EGFR mutations with 100% sensitivity in both plasma and saliva samples, whereas ddPCR detected EGFR mutations with sensitivities of 84.6% and 15.4%, respectively. In saliva samples, the majority of EGFR L858R ctDNA fragments detected were <80 bp. Deep sequencing analysis of ctDNA enriched for the EGFR L858R mutation revealed the significant presence of EGFR L858R ctDNA as ultra-short circulating tumor DNA (usctDNA) with the size of 40–60 bp in patient plasma and saliva. Most of usctDNAs are not amplifiable with the current ddPCR assay. Further examination using cell lines and patient biofluids revealed that the majority of usctDNAs were predominately localized in the exosomal fraction. Our study revealed the abundant existence of EGFR ctDNA in the plasma and saliva of NSCLC patients is usctDNA. usctDNA is a novel type of targets for liquid biopsy that can be efficiently detected by EFIRM technology. MDPI 2020-07-24 /pmc/articles/PMC7464208/ /pubmed/32722209 http://dx.doi.org/10.3390/cancers12082041 Text en © 2020 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
Li, Feng
Wei, Fang
Huang, Wei-Lun
Lin, Chien-Chung
Li, Liang
Shen, Macy M.
Yan, Qingxiang
Liao, Wei
Chia, David
Tu, Michael
Tang, Jason H.
Feng, Ziding
Kim, Yong
Su, Wu-Chou
Wong, David T. W.
Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients
title Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients
title_full Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients
title_fullStr Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients
title_full_unstemmed Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients
title_short Ultra-Short Circulating Tumor DNA (usctDNA) in Plasma and Saliva of Non-Small Cell Lung Cancer (NSCLC) Patients
title_sort ultra-short circulating tumor dna (usctdna) in plasma and saliva of non-small cell lung cancer (nsclc) patients
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7464208/
https://www.ncbi.nlm.nih.gov/pubmed/32722209
http://dx.doi.org/10.3390/cancers12082041
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