Xinyu Zhang1, Zhuo Yu2, Yaping Xu3, Yencheng Chao1, Qin Hu1, Chun Li1, Maosong Ye1, Xiuli Zhu3, Liang Cui3, Jing Bai3, Yuhua Gong3, Yanfang Guan3, Min Zhou4, Jian'an Huang5, Hua Zhang6, Tao Ren7, Qian Shen8, Kai Wang9, Yingyong Hou1, Xuefeng Xia3, Xingxiang Pu10, David P Carbone11, Xin Zhang12. 1. Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, 200032, Shanghai, China. 2. Beijing Tsinghua Changgung Hospital, 168 Litang Road, Changping District, 102218, Beijing, China. 3. Geneplus-Beijing Institute, 9th Floor, No. 6 Building, Peking University Medical Industrial Park, Zhongguancun Life Science Park, 102206, Beijing, China. 4. Ruijin Hospital, Shanghai Jiao Tong University, No. 197 Ruijin Second Road, Huangpu District, 200025, Shanghai, China. 5. First People's Hospital, Suzhou University, No. 899 Pinghai Road, Gusu District, 215008, Suzhou, China. 6. Zhengzhou Central Hospital, Zhengzhou University, No. 195 Tongbai Road, Zhongyuan District, 450000, Zhengzhou, China. 7. Shanghai Sixth People's Hospital, No 600 Yishan Road, Xuhui District, 200233, Shanghai, China. 8. First Affiliated Hospital of Zhejiang University, No. 79 Qingchun Road, Shangcheng District, 310002, Hangzhou, China. 9. Fourth Affiliated Hospital of Zhejiang University, No 88 Jiefang Road, Shangcheng District, 310002, Hangzhou, China. 10. Department of Thoracic Medical Oncology, Hunan Cancer Hospital/the affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, 283 Tongzipo Road, Yuelu District, 410013, Changsha, Hunan, China. pxx_1354@163.com. 11. Comprehensive Cancer Center, The Ohio State University, 460W 12th Ave., Columbus, OH, 43210, USA. David.Carbone@osumc.edu. 12. Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, 200032, Shanghai, China. zhang.xin@zs-hospital.sh.cn.
Abstract
BACKGROUND: Bronchial washing fluid (BWF) is a less-invasive specimen. Due to the limited sensitivity of BWF cellular component diagnosis, the aim of this study was to explore the potential role of BWF supernatant as a source of liquid biopsy of lung cancer. METHODS: This prospective study enrolled 76 suspected and 5 progressed lung cancer patients. Transbronchial biopsy tissues, BWF supernatant (BWF_Sup) and BWF precipitant (BWF_Pre) were tested by a targeted panel of 1021 genes. RESULTS: BWF_Sup cell-free DNA (cfDNA) was superior to tissue biopsy and BWF_Pre in determining mutational allele frequency, tumour mutational burden, and chromosomal instability. Moreover, BWF_Sup and BWF_Pre achieved comparable efficacy to tissue samples in differentiating malignant and benign patients, but only BWF_Sup persisted differentiated performance after excluding 55 malignancies pathologically diagnosed by bronchoscopic biopsy. Among 67 malignant patients, 82.1% and 71.6% of tumour-derived mutations (TDMs) were detected in BWF_Sup and BWF_Pre, respectively, and the detectability of TDMs in BWF_Sup was independent of the cytological examination of BWF. BWF_Sup outperformed BWF_Pre in providing more subclonal information and thus might yield advantage in tracking drug-resistant markers. CONCLUSIONS: BWF_Sup cfDNA is a reliable medium for lung cancer diagnosis and genomic profiles and may provide important information for subsequent therapeutic regimens.
BACKGROUND: Bronchial washing fluid (BWF) is a less-invasive specimen. Due to the limited sensitivity of BWF cellular component diagnosis, the aim of this study was to explore the potential role of BWF supernatant as a source of liquid biopsy of lung cancer. METHODS: This prospective study enrolled 76 suspected and 5 progressed lung cancer patients. Transbronchial biopsy tissues, BWF supernatant (BWF_Sup) and BWF precipitant (BWF_Pre) were tested by a targeted panel of 1021 genes. RESULTS: BWF_Sup cell-free DNA (cfDNA) was superior to tissue biopsy and BWF_Pre in determining mutational allele frequency, tumour mutational burden, and chromosomal instability. Moreover, BWF_Sup and BWF_Pre achieved comparable efficacy to tissue samples in differentiating malignant and benign patients, but only BWF_Sup persisted differentiated performance after excluding 55 malignancies pathologically diagnosed by bronchoscopic biopsy. Among 67 malignant patients, 82.1% and 71.6% of tumour-derived mutations (TDMs) were detected in BWF_Sup and BWF_Pre, respectively, and the detectability of TDMs in BWF_Sup was independent of the cytological examination of BWF. BWF_Sup outperformed BWF_Pre in providing more subclonal information and thus might yield advantage in tracking drug-resistant markers. CONCLUSIONS: BWF_Sup cfDNA is a reliable medium for lung cancer diagnosis and genomic profiles and may provide important information for subsequent therapeutic regimens.
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