Multi-omics integrated circulating cell-free DNA genomic signatures enhanced the diagnostic performance of early-stage lung cancer and postoperative minimal residual diseaseResearch in context
Yun Li,
Guanchao Jiang,
Wendy Wu,
Hao Yang,
Yichen Jin,
Manqi Wu,
Wenjie Liu,
Airong Yang,
Olga Chervova,
Sujie Zhang,
Lu Zheng,
Xueying Zhang,
Fengxia Du,
Nnennaya Kanu,
Lin Wu,
Fan Yang,
Jun Wang,
Kezhong Chen
Affiliations
Yun Li
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing, China
Guanchao Jiang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing, China
Wendy Wu
Berry Oncology Corporation, Beijing, China; Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, China
Hao Yang
Berry Oncology Corporation, Beijing, China
Yichen Jin
Department of Clinical Sciences, Peking University Health Science Center, Beijing, China
Manqi Wu
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing, China
Wenjie Liu
Berry Oncology Corporation, Beijing, China
Airong Yang
Berry Oncology Corporation, Beijing, China
Olga Chervova
University College London Cancer Institute, University College London, 72 Huntley St, London, WC1E 6DD, UK
Sujie Zhang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing, China
Lu Zheng
Berry Oncology Corporation, Beijing, China
Xueying Zhang
Berry Oncology Corporation, Beijing, China
Fengxia Du
Berry Oncology Corporation, Beijing, China
Nnennaya Kanu
University College London Cancer Institute, University College London, 72 Huntley St, London, WC1E 6DD, UK; Cancer Research UK Lung Cancer Centre of Excellence, University College London, 72 Huntley St, London, WC1E 6DD, UK
Lin Wu
Berry Oncology Corporation, Beijing, China; Fujian Key Laboratory of Advanced Technology for Cancer Screening and Early Diagnosis, Fuzhou, China; Corresponding author.
Fan Yang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing, China; Corresponding author.
Jun Wang
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing, China
Kezhong Chen
Thoracic Oncology Institute/Department of Thoracic Surgery, Peking University People's Hospital, Peking University, Beijing, China; Corresponding author.
Summary: Background: Liquid biopsy is a promising non-invasive alternative for cancer screening and minimal residual disease (MRD) detection, although there are some concerns regarding its clinical applications. We aimed to develop an accurate detection platform based on liquid biopsy for both cancer screening and MRD detection in patients with lung cancer (LC), which is also applicable to clinical use. Methods: We applied a modified whole-genome sequencing (WGS) -based High-performance Infrastructure For MultIomics (HIFI) method for LC screening and postoperative MRD detection by combining the hyper-co-methylated read approach and the circulating single-molecule amplification and resequencing technology (cSMART2.0). Findings: For early screening of LC, the LC score model was constructed using the support vector machine, which showed sensitivity (51.8%) at high specificity (96.3%) and achieved an AUC of 0.912 in the validation set prospectively enrolled from multiple centers. The screening model achieved detection efficiency with an AUC of 0.906 in patients with lung adenocarcinoma and outperformed other clinical models in solid nodule cohort. When applied the HIFI model to real social population, a negative predictive value (NPV) of 99.92% was achieved in Chinese population. Additionally, the MRD detection rate improved significantly by combining results from WGS and cSMART2.0, with sensitivity of 73.7% at specificity of 97.3%. Interpretation: In conclusion, the HIFI method is promising for diagnosis and postoperative monitoring of LC. Funding: This study was supported by CAMS Innovation Fund for Medical Sciences, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, Beijing Natural Science Foundation and Peking University People's Hospital.
