Analysis of HOXA9 methylated ctDNA in ovarian cancer using sense-antisense measurement

Louise Faaborg*, Rikke Fredslund Andersen, Marianne Waldstrøm, Estrid Høgdall, Claus Høgdall, Parvin Adimi, Anders Jakobsen, Karina Dahl Steffensen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

DNA promoter methylation is an early event in tumorigenesis and holds promise as a valuable marker in ovarian cancer (OC). It can be measured using circulating tumor specific DNA (ctDNA) isolated from the bloodstream. Sensitivity, however, is a limiting factor of its diagnostic feasibility in OC. DNA methylation analyses are based on bisulfite conversion, resulting in two DNA strands that are no longer complementary. The current standard strategy would then target only one of the double stranded DNA strands, but the potential to increase the sensitivity by targeting both DNA strands is available. In this study, we aimed at evaluating the diagnostic potential of methylated HOXA9 ctDNA in OC by targeting both the DNA sense and antisense strand. Methylated HOXA9 was detected in the plasma of 47/79 (59.5%) patients with newly diagnosed OC using sense-antisense droplet digital PCR. Simultaneous sense-antisense measurement increased the sensitivity by 14.6% (51.9% to 59.5%) as compared to antisense only. In patients with FIGO stage I-II disease the sensitivity was increased by 25%. In conclusion, simultaneous measurement targeting both DNA strands can increase the sensitivity and the analytical approach appears valuable in the diagnostic setting of OC.

Original languageEnglish
JournalClinica Chimica Acta
Volume522
Pages (from-to)152-157
ISSN0009-8981
DOIs
Publication statusPublished - Nov 2021

Bibliographical note

Publisher Copyright:
© 2021 The Authors

Keywords

  • Circulating tumor DNA
  • Droplet digital PCR
  • HOXA9 methylation
  • Ovarian cancer
  • Sense-antisense

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