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Genetics and Genomics

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

British Journal of Cancer volume 127, pages 2154–2165 (2022)Cite this article

Subjects

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.

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Fig. 1: Workflow of samples collection and detection.
Fig. 2: Genomic characteristics of different sample types.
Fig. 3: Genomic discrepancies of different sample types between malignant and non-malignant patients.
Fig. 4: Detection of TDMs in BWF_Sup and BWF_Pre samples.
Fig. 5: TDM detection of cytologically negative BWF.
Fig. 6: Joint clonal analysis of FFPE, BWF_Sup and BWF_Pre.

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Data availability

The datasets supporting the conclusions of this article are available from the corresponding author on reasonable request.

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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

  1. These authors contributed equally: Xinyu Zhang, Zhuo Yu, Yaping Xu.

Authors and Affiliations

  1. 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

  2. Beijing Tsinghua Changgung Hospital, 168 Litang Road, Changping District, 102218, Beijing, China

    Zhuo Yu

  3. 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

  4. Ruijin Hospital, Shanghai Jiao Tong University, No. 197 Ruijin Second Road, Huangpu District, 200025, Shanghai, China

    Min Zhou

  5. First People’s Hospital, Suzhou University, No. 899 Pinghai Road, Gusu District, 215008, Suzhou, China

    Jian’an Huang

  6. Zhengzhou Central Hospital, Zhengzhou University, No. 195 Tongbai Road, Zhongyuan District, 450000, Zhengzhou, China

    Hua Zhang

  7. Shanghai Sixth People’s Hospital, No 600 Yishan Road, Xuhui District, 200233, Shanghai, China

    Tao Ren

  8. First Affiliated Hospital of Zhejiang University, No. 79 Qingchun Road, Shangcheng District, 310002, Hangzhou, China

    Qian Shen

  9. Fourth Affiliated Hospital of Zhejiang University, No 88 Jiefang Road, Shangcheng District, 310002, Hangzhou, China

    Kai Wang

  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

    Xingxiang Pu

  11. Comprehensive Cancer Center, The Ohio State University, 460W 12th Ave., Columbus, OH, 43210, USA

    David P. Carbone

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  1. Xinyu Zhang
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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.

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This study was approved by the Ethics Committee of the Zhongshan Hospital of Fudan University (No. B2018-027) and complied with all relevant ethical regulations. All participating patients signed written informed consent.

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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

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