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The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer

SIMPLE SUMMARY: This study aims to detect cell-free DNA released from lung cancer cells into the airway using the ex vivo BAL model of our own establishing. We finally demonstrated that cell-free DNA released from lung cancer cells is more abundant in the airway than in the blood, and the efficient...

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Autores principales: Otake, Sotaro, Goto, Taichiro, Higuchi, Rumi, Nakagomi, Takahiro, Hirotsu, Yosuke, Amemiya, Kenji, Oyama, Toshio, Mochizuki, Hitoshi, Omata, Masao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996852/
https://www.ncbi.nlm.nih.gov/pubmed/35406535
http://dx.doi.org/10.3390/cancers14071764
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author Otake, Sotaro
Goto, Taichiro
Higuchi, Rumi
Nakagomi, Takahiro
Hirotsu, Yosuke
Amemiya, Kenji
Oyama, Toshio
Mochizuki, Hitoshi
Omata, Masao
author_facet Otake, Sotaro
Goto, Taichiro
Higuchi, Rumi
Nakagomi, Takahiro
Hirotsu, Yosuke
Amemiya, Kenji
Oyama, Toshio
Mochizuki, Hitoshi
Omata, Masao
author_sort Otake, Sotaro
collection PubMed
description SIMPLE SUMMARY: This study aims to detect cell-free DNA released from lung cancer cells into the airway using the ex vivo BAL model of our own establishing. We finally demonstrated that cell-free DNA released from lung cancer cells is more abundant in the airway than in the blood, and the efficient collection of cell-free DNA derived from lung cancer in the airway by BAL and its genomic analysis could allow the accurate diagnosis of lung cancer. We believe that this approach will possibly make a breakthrough in the currently unsatisfactory diagnostic yield for lung cancer, since it is a new and constitutive diagnostic focusing on the gene mutations of lung cancer and their release into the airway in the form of cell-free DNA. ABSTRACT: Although bronchoscopy is generally performed to diagnose lung cancer, its diagnostic yield remains unsatisfactory. Assuming that lung cancer cells release cell-free DNA into the epithelial lining fluid, we hypothesized that lung cancer could be diagnosed by analyzing gene mutations in cell-free DNA in this fluid. This study included 32 patients with lung cancer who underwent surgery at our hospital. Bronchoalveolar lavage (BAL) was performed on the resected lung samples (ex vivo BAL model) after lobectomy. Each DNA sample (i.e., BAL fluid, primary lesion, and plasma) underwent deep targeted sequencing. Gene mutation analyses in the BAL fluid samples identified mutations identical to those in the primary lesions in 30 (93.8%) of 32 patients. In contrast, the microscopic cytology of the same BAL fluid samples yielded a diagnosis of lung cancer in only one of 32 patients, and the analysis of plasma samples revealed gene mutations identical to those in the primary lesions in only one of 32 patients. In conclusion, cell-free DNA released from lung cancer cells exists more abundantly in the airway than in the blood. The collection and analysis of the BAL fluid containing cell-free DNA derived from lung cancer can thus allow lung cancer diagnosis and the screening of driver mutations.
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spelling pubmed-89968522022-04-12 The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer Otake, Sotaro Goto, Taichiro Higuchi, Rumi Nakagomi, Takahiro Hirotsu, Yosuke Amemiya, Kenji Oyama, Toshio Mochizuki, Hitoshi Omata, Masao Cancers (Basel) Article SIMPLE SUMMARY: This study aims to detect cell-free DNA released from lung cancer cells into the airway using the ex vivo BAL model of our own establishing. We finally demonstrated that cell-free DNA released from lung cancer cells is more abundant in the airway than in the blood, and the efficient collection of cell-free DNA derived from lung cancer in the airway by BAL and its genomic analysis could allow the accurate diagnosis of lung cancer. We believe that this approach will possibly make a breakthrough in the currently unsatisfactory diagnostic yield for lung cancer, since it is a new and constitutive diagnostic focusing on the gene mutations of lung cancer and their release into the airway in the form of cell-free DNA. ABSTRACT: Although bronchoscopy is generally performed to diagnose lung cancer, its diagnostic yield remains unsatisfactory. Assuming that lung cancer cells release cell-free DNA into the epithelial lining fluid, we hypothesized that lung cancer could be diagnosed by analyzing gene mutations in cell-free DNA in this fluid. This study included 32 patients with lung cancer who underwent surgery at our hospital. Bronchoalveolar lavage (BAL) was performed on the resected lung samples (ex vivo BAL model) after lobectomy. Each DNA sample (i.e., BAL fluid, primary lesion, and plasma) underwent deep targeted sequencing. Gene mutation analyses in the BAL fluid samples identified mutations identical to those in the primary lesions in 30 (93.8%) of 32 patients. In contrast, the microscopic cytology of the same BAL fluid samples yielded a diagnosis of lung cancer in only one of 32 patients, and the analysis of plasma samples revealed gene mutations identical to those in the primary lesions in only one of 32 patients. In conclusion, cell-free DNA released from lung cancer cells exists more abundantly in the airway than in the blood. The collection and analysis of the BAL fluid containing cell-free DNA derived from lung cancer can thus allow lung cancer diagnosis and the screening of driver mutations. MDPI 2022-03-30 /pmc/articles/PMC8996852/ /pubmed/35406535 http://dx.doi.org/10.3390/cancers14071764 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/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 (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Otake, Sotaro
Goto, Taichiro
Higuchi, Rumi
Nakagomi, Takahiro
Hirotsu, Yosuke
Amemiya, Kenji
Oyama, Toshio
Mochizuki, Hitoshi
Omata, Masao
The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer
title The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer
title_full The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer
title_fullStr The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer
title_full_unstemmed The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer
title_short The Diagnostic Utility of Cell-Free DNA from Ex Vivo Bronchoalveolar Lavage Fluid in Lung Cancer
title_sort diagnostic utility of cell-free dna from ex vivo bronchoalveolar lavage fluid in lung cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8996852/
https://www.ncbi.nlm.nih.gov/pubmed/35406535
http://dx.doi.org/10.3390/cancers14071764
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