Validating methylated HOXA9 in bronchial lavage as a diagnostic tool in patients suspected of lung cancer

Sara W.C. Wen*, Rikke F. Andersen, Kristian Rasmussen*, Caroline Brenner Thomsen, Torben Frøstrup Hansen, Line Nederby, Henrik Hager, Anders Jakobsen, Ole Hilberg

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

Diagnosing lung cancer requires invasive procedures with high risk of complications. Methylated tumor DNA in bronchial lavage has previously shown potential as a diagnostic biomarker. We aimed to develop and validate methylated HOXA9 in bronchial lavage as a diagnostic biomarker of lung cancer. Participants were referred on suspicion of lung cancer. Ten mL lavage fluid was collected at bronchoscopy for analysis of methylated HOXA9 based on droplet digital PCR according to our previously published method. HOXA9 status was compared with the final diagnosis. The Discovery and Validation cohorts consisted of 101 and 95 consecutively enrolled participants, re-spectively. In the discovery cohort, the sensitivity and specificity were 73.1% (95% CI 60.9–83.2%) and 85.3% (95% CI 68.9–95.0%), respectively. In the validation cohort, the values were 80.0% (95% CI 66.3–90.0%) and 75.6% (95% CI 60.5–87.1%), respectively. A multiple logistic regression model including age, smoking status, and methylated HOXA9 status resulted in an AUC of 84.9% (95% CI 77.3–92.4%) and 85.9% (95% CI 78.4–93.4%) for the Discovery and Validation cohorts, respectively. Methylated HOXA9 in bronchial lavage holds potential as a supplementary tool in the diagnosis of lung cancer with a clinically relevant sensitivity and specificity. It remained significant when adjusting for age and smoking status.

Original languageEnglish
Article number4223
JournalCancers
Volume13
Issue number16
Number of pages12
ISSN2072-6694
DOIs
Publication statusPublished - 2. Aug 2021

Bibliographical note

Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.

Keywords

  • Circulating tumor DNA
  • Lung cancer
  • Methylated HOXA9

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