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

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

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

Author: Changdan XU ¹ ; Xiaohong XU ² ; Weipeng SHAO ³ ; Hongliang SUN ⁴ ; Xiaohong LIU ⁵ ; Hongxiang FENG ³ ; Xianbo ZUO ⁶ ; Jingyang GAO ⁵ ; Guohui WANG ⁷ ; Xiongtao YANG ⁸ ; Runchuan GU ⁹ ; Shutong GE ¹ ; Shijie WANG ¹⁰ ; Liwei GAO ¹¹ ; Guangying ZHU ¹
Author Information

1. Department of Radiation Oncology, Peking University China-Japan Friendship School of Clinical Medicine, Beijing 100029, China.
2. Department of Radiation Oncology, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
3. Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
4. Department of Radiology, China-Japan Friendship Hospital, Beijing 100029, China.
5. Department of Information Science and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
6. Department of Dermatology, China-Japan Friendship Hospital, Beijing 100029, China.
7. Department of Radiation Oncology, Tianjin First Central Hospital, Tianjin 300070, China.
8. Department of Oncology, Beijing Changping District Hospital, Beijing 102200, China.
9. Faculty of Medicine Lund University, Lund SE-22100, Sweden.
10. Department of Radiation Oncology, China-Japan Friendship Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100029, China.
11. Department of Radiation Oncology, Center of Respiratory Medicine, China-Japan Friendship Hospital, Beijing 100029, China.
Publication Type:Journal Article
MeSH: Humans; Lung Neoplasms; Exome Sequencing; Multiple Pulmonary Nodules; Carcinoma; DNA Repair
From: Chinese Journal of Lung Cancer 2023;26(6):449-460
CountryChina
Language:English
Abstract: BACKGROUND: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.
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.
CONCLUSIONS: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.