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Updated: Jun 16, 2025
Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Non-invasive diagnosis of pulmonary nodules by circulating tumor DNA methylation: A prospective multicenter study
Ying Li1, Fangfang Xie1, Qiang Zheng2
1Department of Respiratory Endoscopy, Department of Respiratory and Critical Care Medicine, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Engineering Research Center of Respiratory Endoscopy, Shanghai, China.
Background:
With the popularization of computed tomography, more and more pulmonary nodules (PNs) are being detected. Risk stratification of PNs is essential for detecting early-stage lung cancer while minimizing the overdiagnosis of benign nodules. This study aimed to develop a circulating tumor DNA (ctDNA) methylation-based, non-invasive model for the risk stratification of PNs.
Methods:
A blood-based assay ("LUNG-TRAC") was designed to include novel lung cancer ctDNA methylation markers identified from in-house reduced representative bisulfite sequencing data and known markers from the literature. A stratification model was trained based on 183 ctDNA samples derived from patients with benign or malignant PNs and validated in 62 patients. LUNG-TRAC was further single-blindly tested in a single- and multi-center cohort.
Results:
The LUNG-TRAC model achieved an area under the curve (AUC) of 0.810 (sensitivity = 74.4 % and specificity = 73.7 %) in the validation set. Two test sets were used to evaluate the performance of LUNG-TRAC, with an AUC of 0.815 in the single-center test (N = 61; sensitivity = 67.5 % and specificity = 76.2 %) and 0.761 in the multi-center test (N = 95; sensitivity = 50.7 % and specificity = 80.8 %). The clinical utility of LUNG-TRAC was further assessed by comparing it to two established risk stratification models: the Mayo Clinic and Veteran Administration models. It outperformed both in the validation and the single-center test sets.
Conclusion:
The LUNG-TRAC model demonstrated accuracy and consistency in stratifying PNs for the risk of malignancy, suggesting its utility as a non-invasive diagnostic aid for early-stage peripheral lung cancer.
Clinical Trial Registration:
www.
Clinicaltrials:
gov (NCT03989219).
