Cell Free Methylated Tumor DNA in Bronchial Lavage as an Additional Tool for Diagnosing Lung Cancer: A Systematic Review

Sara Witting Christensen Wen*, Jan Wen, Torben Frøstrup Hansen, Anders Jakobsen, Ole Hilberg

*Corresponding author for this work

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This systematic review investigated circulating methylated tumor DNA in bronchial lavage fluid for diagnosing lung cancer. PROSPERO registration CRD42022309470. PubMed, Embase, Medline, and Web of Science were searched on 9 March 2022. Studies of adults with lung cancer or undergoing diagnostic workup for suspected lung cancer were included if they used bronchial lavage fluid, analyzed methylated circulating tumor DNA, and reported the diagnostic properties. Sensitivity, specificity, and lung cancer prevalence were summarized in forest plots. Risk of bias was assessed using the QUADAS-2 tool. A total of 25 studies were included. All were case-control studies, most studies used cell pellet for analysis by quantitative PCR. Diagnostic sensitivity ranged from 0% for a single gene to 97% for a four-gene panel. Specificity ranged from 8% for a single gene to 100%. The studies employing a gene panel decreased the specificity, and no gene panel had a perfect specificity of 100%. In conclusion, methylated circulating tumor DNA can be detected in bronchial lavage, and by employing a gene panel the sensitivity can be increased to clinically relevant levels. The available evidence regarding applicability in routine clinical practice is limited. Prospective, randomized clinical trials are needed to determine the further usefulness of this biomarker.

Original languageEnglish
Article number2254
Issue number9
Number of pages13
Publication statusPublished - 30. Apr 2022

Bibliographical note

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© 2022 by the authors. Licensee MDPI, Basel, Switzerland.


  • bronchial lavage
  • bronchial wash
  • circulating tumor DNA
  • ctDNA
  • DNA methylation
  • lung cancer


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