Multi-omics integrated circulating cell-free DNA genomic signatures enhanced the diagnostic performance of early-stage lung cancer and postoperative minimal residual disease

液体活检 医学 阶段(地层学) 内科学 肿瘤科 人口 肺癌 微小残留病 癌症 生物 古生物学 环境卫生 白血病
作者
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
出处
期刊:EBioMedicine [Elsevier BV]
卷期号:91: 104553-104553 被引量:29
标识
DOI:10.1016/j.ebiom.2023.104553
摘要

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.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).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%.In conclusion, the HIFI method is promising for diagnosis and postoperative monitoring of LC.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.
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