Prognostic Impact of Circulating Methylated Homeobox A9 DNA in Patients Undergoing Treatment for Recurrent Ovarian Cancer

Louise Faaborg*, Rikke Fredslund Andersen, Marianne Waldstrøm, Jon Røikjær Henriksen, Parvin Adimi, Anders Jakobsen, Karina Dahl Steffensen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Methylated Homeobox A9 circulating tumor DNA (meth-HOXA9) has been suggested as a blood-based biomarker in epithelial ovarian cancer (EOC), although its prognostic significance remains unproven. The aim of the present study was to investigate the prognostic impact of meth-HOXA9 in patients with recurrent EOC. DNA was purified from 4 mL plasma and, following bilsulfite conversion, meth-HOXA9 was analyzed using a methylation-specific droplet digital PCR. Detection of meth-HOXA9 was reported as a percentage of total DNA and as a binary variable (detectable and undetectable). Meth-HOXA9 status and its dynamics during palliative treatment were correlated with overall survival (OS) as the primary endpoint. At baseline, meth-HOXA9 was detected in 65.9% (83/126) of the patients. The median OS was 8.9 and 17.9 months in patients with detectable and undetectable meth-HOXA9 at baseline (hazard ratio: 2.04, p = 0.002), which remained significant in the multivariate analysis. Median OS in patients with an increase in meth-HOXA9 after one treatment cycle was 5.3 months compared to 33 months in patients with undetectable meth-HOXA9 (p < 0.001). Meth-HOXA9 was significantly related to poor survival and may serve as a prognostic marker in patients with recurrent EOC. The longitudinal monitoring of meth-HOXA9 is clinically feasible with the perspective of aiding clinical decision making.

Original languageEnglish
Article number1766
Issue number7
Number of pages12
Publication statusPublished - 30. Mar 2022

Bibliographical note

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


  • biomarker
  • circulating tumor DNA
  • Homeobox A9
  • liquid biopsy
  • methylation
  • ovarian cancer
  • prognosis
  • relapse


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