CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules

Background and objective Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of...

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Main Authors: Changdan XU, Xiaohong XU, Weipeng SHAO, Hongliang SUN, Xiaohong LIU, Hongxiang FENG, Xianbo ZUO, Jingyang GAO, Guohui WANG, Xiongtao YANG, Runchuan GU, Shutong GE, Shijie WANG, Liwei GAO, Guangying ZHU
Format: Article
Language:zho
Published: Chinese Anti-Cancer Association; Chinese Antituberculosis Association 2023-06-01
Series:Chinese Journal of Lung Cancer
Subjects:
Online Access:http://dx.doi.org/10.3779/j.issn.1009-3419.2023.106.12
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author Changdan XU
Xiaohong XU
Weipeng SHAO
Hongliang SUN
Xiaohong LIU
Hongxiang FENG
Xianbo ZUO
Jingyang GAO
Guohui WANG
Xiongtao YANG
Runchuan GU
Shutong GE
Shijie WANG
Liwei GAO
Guangying ZHU
author_facet Changdan XU
Xiaohong XU
Weipeng SHAO
Hongliang SUN
Xiaohong LIU
Hongxiang FENG
Xianbo ZUO
Jingyang GAO
Guohui WANG
Xiongtao YANG
Runchuan GU
Shutong GE
Shijie WANG
Liwei GAO
Guangying ZHU
author_sort Changdan XU
collection DOAJ
description Background and objective Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. 
Materials and methods 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. 
Results Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. 
Conclusion CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.
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spelling doaj.art-386f38207981411d9062f15fc278fa332023-07-25T01:53:49ZzhoChinese Anti-Cancer Association; Chinese Antituberculosis AssociationChinese Journal of Lung Cancer1009-34191999-61872023-06-0126644946010.3779/j.issn.1009-3419.2023.106.12CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary NodulesChangdan XU0Xiaohong XU1Weipeng SHAO2Hongliang SUN3Xiaohong LIU4Hongxiang FENG5Xianbo ZUO6Jingyang GAO7Guohui WANG8Xiongtao YANG9Runchuan GU10Shutong GE11Shijie WANG12Liwei GAO13Guangying ZHU14Department of Radiation Oncology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, ChinaDepartment of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, ChinaDepartment of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Radiology, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Information Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaDepartment of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Dermatology, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Information Science and Technology, Beijing University of Chemical Technology, Beijing 100029, ChinaDepartment of Radiation Oncology, Tianjin First Central Hospital, Tianjin 300070, ChinaDepartment of Oncology, Beijing Changping District Hospital, Beijing 102200, ChinaFaculty of Medicine Lund University, Lund SE-22100, SwedenDepartment of Radiation Oncology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, ChinaDepartment of Radiation Oncology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, ChinaDepartment of Radiation Oncology, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, ChinaDepartment of Radiation Oncology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, ChinaBackground and objective Low-density computed tomography (LDCT) improved early lung cancer diagnosis but introduces an excess of false-positive pulmonary nodules data. Hence, accurate diagnosis of early-stage lung cancer remains challenging. The purpose of the study was to assess the feasibility of using circulating tumour cells (CTCs) to differentiate malignant from benign pulmonary nodules. 
Materials and methods 122 patients with suspected malignant pulmonary nodules detected on chest CT in preparation for surgery were prospectively recruited. Peripheral blood samples were collected before surgery, and CTCs were identified upon isolation by size of epithelial tumour cells and morphological analysis. Laser capture microdissection, MALBAC amplification, and whole-exome sequencing were performed on 8 samples. The diagnostic efficacy of CTCs counting, and the genomic variation profile of benign and malignant CTCs samples were analysed. 
Results Using 2.5 cells/5 mL as the cut-off value, the area under the receiver operating characteristic curve was of 0.651 (95% confidence interval: 0.538-0.764), with a sensitivity and specificity of 0.526 and 0.800, respectively, and positive and negative predictive values of 91.1% and 30.3%, respectively. Distinct sequence variations differences in DNA damage repair-related and driver genes were observed in benign and malignant samples. TP53 mutations were identified in CTCs of four malignant cases; in particular, g.7578115T>C, g.7578645C>T, and g.7579472G>C were exclusively detected in all four malignant samples. 
Conclusion CTCs play an ancillary role in the diagnosis of pulmonary nodules. TP53 mutations in CTCs might be used to identify benign and malignant pulmonary nodules.http://dx.doi.org/10.3779/j.issn.1009-3419.2023.106.12chest computed tomographycirculating tumour cellslung noduletp53whole-exome sequencing
spellingShingle Changdan XU
Xiaohong XU
Weipeng SHAO
Hongliang SUN
Xiaohong LIU
Hongxiang FENG
Xianbo ZUO
Jingyang GAO
Guohui WANG
Xiongtao YANG
Runchuan GU
Shutong GE
Shijie WANG
Liwei GAO
Guangying ZHU
CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules
Chinese Journal of Lung Cancer
chest computed tomography
circulating tumour cells
lung nodule
tp53
whole-exome sequencing
title CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules
title_full CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules
title_fullStr CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules
title_full_unstemmed CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules
title_short CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules
title_sort ctcs detection and whole exome sequencing might be used to differentiate benign and malignant pulmonary nodules
topic chest computed tomography
circulating tumour cells
lung nodule
tp53
whole-exome sequencing
url http://dx.doi.org/10.3779/j.issn.1009-3419.2023.106.12
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