Cell-free DNA from bronchoalveolar lavage fluid (BALF): a new liquid biopsy medium for identifying lung cancer

Daxiong Zeng; Cangguo Wang; Chuanyong Mu; Meiqin Su; Jingyu Mao; Jianan Huang; Jiayue Xu; Lin Shao; Bing Li; Haiyan Li; Bingsi Li; Jun Zhao; Junhong Jiang

doi:10.21037/atm-21-2579

Cell-free DNA from bronchoalveolar lavage fluid (BALF): a new liquid biopsy medium for identifying lung cancer

Ann Transl Med. 2021 Jul;9(13):1080. doi: 10.21037/atm-21-2579.

Authors

Daxiong Zeng^{1

2}, Cangguo Wang², Chuanyong Mu², Meiqin Su², Jingyu Mao², Jianan Huang², Jiayue Xu³, Lin Shao³, Bing Li³, Haiyan Li³, Bingsi Li³, Jun Zhao⁴, Junhong Jiang^{1

2}

Affiliations

¹ Department of Respiratory Medicine, Dusu Lake Hospital to Soochow University, Suzhou, China.
² Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, China.
³ Burning Rock Biotech, Guangzhou, China.
⁴ Department of Thoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, China.

Abstract

Background: Differentiating malignant lung tumors from benign pulmonary nodules is a great challenge. While the analysis of bronchoalveolar lavage fluid (BALF) is used for diagnosing infections and interstitial lung diseases, there is limited evidence to support its use for lung cancer diagnosis. This study aimed to interrogate the potential of using BALF cell-free DNA (cfDNA) to discriminate malignant lesions from benign nodules.

Methods: Fifty-three patients with solid pulmonary nodules (≤2 cm) were prospectively enrolled, including 21 confirmed with benign disease and 32 with malignant tumors. Mutations were profiled for 30 tumor tissues and 40 BALFs. Paired BALFs and plasma from 48 patients underwent DNA methylation profiling. A methylome-based classification model was developed for BALF and plasma separately.

Results: Among the 30 patients with paired tissues and BALFs, 96.7% and 70% had alterations detected from their tissues (79 alterations) and BALFs (53 alterations), respectively. Using tissues as references, BALFs revealed 14 new alterations and missed 41. BALF mutation displayed a sensitivity of 71%, specificity of 77.8%, and accuracy of 72.5% in detecting lung cancer. BALF methylation achieved an accuracy of 81.3%, with both sensitivity and specificity being 81%. Plasma methylation showed a 66.7% sensitivity, 71.4% specificity, and 68.8% accuracy. BALF methylation also demonstrated 82.4% sensitivity in stage I patients. Parallel bronchoscopy, lavage cytology, and bronchial brushing demonstrated an inferior sensitivity of 23%, 3.1%, and 9.7%, respectively, compared with BALF methylation and mutation (P<0.0001).

Conclusions: BALF cfDNA can serve as a liquid biopsy media for both mutation and methylation profiling, demonstrating better sensitivities in distinguishing small malignant tumors from benign nodules than conventional methods.

Keywords: Lung cancer diagnosis; pulmonary nodule; bronchoalveolar lavage fluid (BALF); methylation; genomic mutation.