Lung tumor discrimination by deep neural network model CanDo via DNA methylation in bronchial lavage
Zezhong Yu,
Jieyi Li,
Yi Deng,
Chun Li,
Maosong Ye,
Yong Zhang,
Yuqing Huang,
Xintao Wang,
Xiaokai Zhao,
Jie Liu,
Zilong Liu,
Xia Yin,
Lijiang Mei,
Yingyong Hou,
Qin Hu,
Yao Huang,
Rongping Wang,
Huiyu Fu,
Rumeng Qiu,
Jiahuan Xu,
Ziying Gong,
Daoyun Zhang,
Xin Zhang
Affiliations
Zezhong Yu
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Jieyi Li
Jiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing 314033, China; Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China
Yi Deng
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Chun Li
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Maosong Ye
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Yong Zhang
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Yuqing Huang
Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China
Xintao Wang
Jiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing 314033, China; Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China
Xiaokai Zhao
Jiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing 314033, China; Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China
Jie Liu
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Zilong Liu
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Xia Yin
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Lijiang Mei
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Yingyong Hou
Department of Pathology Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Qin Hu
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China
Yao Huang
Department of Pulmonary, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210046, China
Rongping Wang
Department of Pulmonary, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210046, China
Huiyu Fu
Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China
Rumeng Qiu
Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China
Jiahuan Xu
Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China
Ziying Gong
Jiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing 314033, China; Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China; Department of R&D, Shanghai Yunying Biopharmaceutical Technology Co., Ltd., Shanghai 201612, China; Corresponding author
Daoyun Zhang
Jiaxing Key Laboratory of Precision Medicine and Companion Diagnostics, Jiaxing Yunying Medical Inspection Co., Ltd., Jiaxing 314033, China; Department of R&D, Zhejiang Yunying Medical Technology Co., Ltd., Jiaxing 314006, China; Department of R&D, Shanghai Yunying Biopharmaceutical Technology Co., Ltd., Shanghai 201612, China; Corresponding author
Xin Zhang
Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China; Department of Pulmonary, Taikang Xianlin Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210046, China; Corresponding author
Summary: Bronchoscopic-assisted discrimination of lung tumors presents challenges, especially in cases with contraindications or inaccessible lesions. Through meta-analysis and validation using the HumanMethylation450 database, this study identified methylation markers for molecular discrimination in lung tumors and designed a sequencing panel. DNA samples from 118 bronchial washing fluid (BWF) specimens underwent enrichment via multiplex PCR before targeted methylation sequencing. The Recursive Feature Elimination Cross-Validation and deep neural network algorithm established the CanDo classification model, which incorporated 11 methylation features (including 8 specific to the TBR1 gene), demonstrating a sensitivity of 98.6% and specificity of 97.8%. In contrast, bronchoscopic rapid on-site evaluation (bronchoscopic-ROSE) had lower sensitivity (87.7%) and specificity (80%). Further validation in 33 individuals confirmed CanDo’s discriminatory potential, particularly in challenging cases for bronchoscopic-ROSE due to pathological complexity. CanDo serves as a valuable complement to bronchoscopy for the discriminatory diagnosis and stratified management of lung tumors utilizing BWF specimens.
