Utility of cell-free dna from bronchial washing fluid in diagnosis and genomic determination for radiology-suspected pulmonary nodules

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. Access through your institution Buy or

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PROPOSAL OF A NOVEL PIPELINE INVOLVING PRECISE BRONCHOSCOPY OF DISTAL PERIPHERAL PULMONARY LESIONS FOR GENETIC TESTING Article Open access 17 November 2022 COMPARATIVE ANALYSIS OF EGFR

MUTATIONS IN CIRCULATING TUMOR DNA AND PRIMARY TUMOR TISSUES FROM LUNG CANCER PATIENTS USING BEAM_ING_ PCR Article Open access 08 January 2025 MOLECULAR CHARACTERISTICS OF PRIMARY PULMONARY

LYMPHOEPITHELIOMA-LIKE CARCINOMA BASED ON INTEGRATED GENOMIC ANALYSES Article Open access 08 January 2021 DATA AVAILABILITY The datasets supporting the conclusions of this article are

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Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS Prior abstract presentation: Oral presentation, Tumour-derived cell-free DNA from bronchoalveolar

lavage fluid (BALF): a potential liquid biopsy analysis in lung cancer patients; April 3, 2019, American Association for Cancer Research (AACR) Annual Meeting, Atlanta, USA. FUNDING None.

AUTHOR INFORMATION Author notes * These authors contributed equally: Xinyu Zhang, Zhuo Yu, Yaping Xu. AUTHORS AND AFFILIATIONS * Zhongshan Hospital, Fudan University, No. 180 Fenglin Road,

Xuhui District, 200032, Shanghai, China Xinyu Zhang, Yencheng Chao, Qin Hu, Chun Li, Maosong Ye, Yingyong Hou & Xin Zhang * Beijing Tsinghua Changgung Hospital, 168 Litang Road,

Changping District, 102218, Beijing, China Zhuo Yu * Geneplus-Beijing Institute, 9th Floor, No. 6 Building, Peking University Medical Industrial Park, Zhongguancun Life Science Park, 102206,

Beijing, China Yaping Xu, Xiuli Zhu, Liang Cui, Jing Bai, Yuhua Gong, Yanfang Guan & Xuefeng Xia * Ruijin Hospital, Shanghai Jiao Tong University, No. 197 Ruijin Second Road, Huangpu

District, 200025, Shanghai, China Min Zhou * First People’s Hospital, Suzhou University, No. 899 Pinghai Road, Gusu District, 215008, Suzhou, China Jian’an Huang * Zhengzhou Central

Hospital, Zhengzhou University, No. 195 Tongbai Road, Zhongyuan District, 450000, Zhengzhou, China Hua Zhang * Shanghai Sixth People’s Hospital, No 600 Yishan Road, Xuhui District, 200233,

Shanghai, China Tao Ren * First Affiliated Hospital of Zhejiang University, No. 79 Qingchun Road, Shangcheng District, 310002, Hangzhou, China Qian Shen * Fourth Affiliated Hospital of

Zhejiang University, No 88 Jiefang Road, Shangcheng District, 310002, Hangzhou, China Kai Wang * 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 Xingxiang Pu * Comprehensive Cancer Center, The Ohio State

University, 460W 12th Ave., Columbus, OH, 43210, USA David P. Carbone Authors * Xinyu Zhang View author publications You can also search for this author inPubMed Google Scholar * Zhuo Yu

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View author publications You can also search for this author inPubMed Google Scholar CONTRIBUTIONS Prof. Xin Zhang is the guarantor of the content of the manuscript, including the data and

analysis. Xinyu Zhang and YX had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. ZY, Yencheng Chao,

QH, CL, MY, X Zhu, LC, JB, Y Gong, Y Guan, MZ, JH, HZ, TR, QS, KW, YH, XX, DPC and XP contributed substantially to the study design, data analysis and interpretation, and the writing of the

manuscript. CORRESPONDING AUTHORS Correspondence to Xingxiang Pu, David P. Carbone or Xin Zhang. ETHICS DECLARATIONS COMPETING INTERESTS The authors declare no competing interests. ETHICS

APPROVAL AND CONSENT TO PARTICIPATE This study was approved by the Ethics Committee of the Zhongshan Hospital of Fudan University (No. B2018-027) and complied with all relevant ethical

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CITE THIS ARTICLE Zhang, X., Yu, Z., Xu, Y. _et al._ Utility of cell-free DNA from bronchial washing fluid in diagnosis and genomic determination for radiology-suspected pulmonary nodules.

_Br J Cancer_ 127, 2154–2165 (2022). https://doi.org/10.1038/s41416-022-01969-2 Download citation * Received: 12 July 2021 * Revised: 05 July 2022 * Accepted: 23 August 2022 * Published: 17

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