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Non-invasive lung cancer diagnosis and prognosis based on multi-analyte liquid biopsy

By Kezhong Chen, Jianlong Sun, Heng Zhao, Ruijingfang Jiang, Jianchao Zheng, Zhilong Li, Jiaxi Peng, Haifeng Shen, Kai Zhang, Jin Zhao, Shida Zhu, Yuying Wang, Fan Yang, Jun Wang

Posted 23 Aug 2020
medRxiv DOI: 10.1101/2020.08.20.20179044

Chest LDCT provides an effective approach for lung cancer screening, yet has been found to generate a large number of false positives during practice due to excessive diagnosis of pulmonary lesions of indeterminate clinical significance. In this study, we performed comprehensive genetic and epigenetic profiling of cfDNA from lung cancer patients and individuals bearing benign lung lesions, using ultra-deep targeted sequencing and targeted bisulfite sequencing. We found that cfDNA mutation profile alone has relatively limited power in distinguishing malignant from benign plasma, while cfDNA methylation profiling showed a better performance for classification of the two groups and combination of genetic and epigenetic features of cfDNA along with serum protein marker further improved the classification accuracy. We also identified novel methylation-based prognostic markers and showed that an integrated model that combined cfDNA mutational status and methylation-based prognostic markers improved prediction for lung cancer survival. Our results highlight the potential of the multi-analyte assay for non-invasive lung cancer diagnosis and prognosis.

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