Early detection and stratification of lung cancer aided by a cost-effective assay targeting circulating tumor DNA (ctDNA) methylation

Respiratory Research

Correspondence

Chengpin Li¹  Jun Tang¹  Yangqian Li¹  Dan Liu¹  Xue Xiao¹  Zhoufeng Wang¹  Cheng Cheng¹  Guonian Zhu¹  Weimin Li²  Yan Huang³  Huairong Tang³  Wengeng Zhang⁴  Rui Liu⁵  Chengcheng Ma⁵  Zhixi Su⁵  Kehui Xie⁵  Hui Wang⁵ 

[1] Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China;Department of Respiratory and Critical Care Medicine, Institute of Respiratory Health, Frontiers Science Center for Disease-related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan, China;Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China;Health Management Center, West China Hospital, Sichuan University, Chengdu, Sichuan, China;Precision Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu, Sichuan, China;Singlera Genomics (Shanghai) Ltd, Shanghai, China;

关键词: Lung cancer;    Early detection;    Circulating tumor DNA;    Methylation;    qPCR assay;   

DOI  :  10.1186/s12931-023-02449-8

 received in 2022-10-26, accepted in 2023-05-12,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundDetection of lung cancer at earlier stage can greatly improve patient survival. We aim to develop, validate, and implement a cost-effective ctDNA-methylation-based plasma test to aid lung cancer early detection.MethodsCase-control studies were designed to select the most relevant markers to lung cancer. Patients with lung cancer or benign lung disease and healthy individuals were recruited from different clinical centers. A multi-locus qPCR assay, LunaCAM, was developed for lung cancer alertness by ctDNA methylation. Two LunaCAM models were built for screening (-S) or diagnostic aid (-D) to favor sensitivity or specificity, respectively. The performance of the models was validated for different intended uses in clinics.ResultsProfiling DNA methylation on 429 plasma samples including 209 lung cancer, 123 benign diseases and 97 healthy participants identified the top markers that detected lung cancer from benign diseases and healthy with an AUC of 0.85 and 0.95, respectively. The most effective methylation markers were verified individually in 40 tissues and 169 plasma samples to develop LunaCAM assay. Two models corresponding to different intended uses were trained with 513 plasma samples, and validated with an independent collection of 172 plasma samples. In validation, LunaCAM-S model achieved an AUC of 0.90 (95% CI: 0.88–0.94) between lung cancer and healthy individuals, whereas LunaCAM-D model stratified lung cancer from benign pulmonary diseases with an AUC of 0.81 (95% CI: 0.78–0.86). When implemented sequentially in the validation set, LunaCAM-S enables to identify 58 patients of lung cancer (90.6% sensitivity), followed by LunaCAM-D to remove 20 patients with no evidence of cancer (83.3% specificity). LunaCAM-D significantly outperformed the blood test of carcinoembryonic antigen (CEA), and the combined model can further improve the predictive power for lung cancer to an overall AUC of 0.86.ConclusionsWe developed two different models by ctDNA methylation assay to sensitively detect early-stage lung cancer or specifically classify lung benign diseases. Implemented at different clinical settings, LunaCAM models has a potential to provide a facile and inexpensive avenue for early screening and diagnostic aids for lung cancer.

【 授权许可】

CC BY   
© The Author(s) 2023

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