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

Xu, Changdan ; Xu, Xiaohong ; Shao, Weipeng ; Sun, Hongliang ; Liu, Xiaohong ; Feng, Hongxiang ; Zuo, Xianbo ; Gao, Jingyang ; Wang, Guohui and Yang, Xiongtao , et al. (2023) In Chinese Journal of Lung Cancer 26(6). p.449-460
Abstract

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,... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
Chest computed tomography, Circulating tumour cells, Lung nodule, TP53, Whole-exome sequencing
in
Chinese Journal of Lung Cancer
volume
26
issue
6
pages
12 pages
publisher
Chinese Journal of Lung Cancer
external identifiers
  • pmid:37488082
  • scopus:85165744520
ISSN
1009-3419
DOI
10.3779/j.issn.1009-3419.2023.106.12
language
English
LU publication?
yes
id
7bf7810d-91d7-40ab-88e6-0f7a87e0b592
date added to LUP
2023-11-21 15:53:57
date last changed
2024-04-18 19:16:59
@article{7bf7810d-91d7-40ab-88e6-0f7a87e0b592,
  abstract     = {{<p>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&gt;C, g.7578645C&gt;T, and g.7579472G&gt;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.</p>}},
  author       = {{Xu, Changdan and Xu, Xiaohong and Shao, Weipeng and Sun, Hongliang and Liu, Xiaohong and Feng, Hongxiang and Zuo, Xianbo and Gao, Jingyang and Wang, Guohui and Yang, Xiongtao and Gu, Runchuan and Ge, Shutong and Wang, Shijie and Gao, Liwei and Zhu, Guangying}},
  issn         = {{1009-3419}},
  keywords     = {{Chest computed tomography; Circulating tumour cells; Lung nodule; TP53; Whole-exome sequencing}},
  language     = {{eng}},
  number       = {{6}},
  pages        = {{449--460}},
  publisher    = {{Chinese Journal of Lung Cancer}},
  series       = {{Chinese Journal of Lung Cancer}},
  title        = {{CTCs Detection and Whole-exome Sequencing Might Be Used to Differentiate Benign and Malignant Pulmonary Nodules}},
  url          = {{http://dx.doi.org/10.3779/j.issn.1009-3419.2023.106.12}},
  doi          = {{10.3779/j.issn.1009-3419.2023.106.12}},
  volume       = {{26}},
  year         = {{2023}},
}