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

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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.

OriginalsprogEngelsk
TidsskriftClinica Chimica Acta
Vol/bind522
Sider (fra-til)152-157
Antal sider6
ISSN0009-8981
DOI
StatusUdgivet - 2021

Bibliografisk note

Funding Information:
This work was financially supported by the Department of Oncology, Vejle Hospital, Lillebaelt Hospital - University Hospital of Southern Denmark, The Region of Southern Denmark (19/15008) and the NEYE Foundation, Denmark.

Publisher Copyright:
© 2021 The Authors

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