Analysis of HOXA9 methylated ctDNA in ovarian cancer using sense-antisense measurement
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Analysis of HOXA9 methylated ctDNA in ovarian cancer using sense-antisense measurement. / Faaborg, Louise; Fredslund Andersen, Rikke; Waldstrøm, Marianne; Høgdall, Estrid; Høgdall, Claus; Adimi, Parvin; Jakobsen, Anders; Dahl Steffensen, Karina.
I: Clinica Chimica Acta, Bind 522, 2021, s. 152-157.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Analysis of HOXA9 methylated ctDNA in ovarian cancer using sense-antisense measurement
AU - Faaborg, Louise
AU - Fredslund Andersen, Rikke
AU - Waldstrøm, Marianne
AU - Høgdall, Estrid
AU - Høgdall, Claus
AU - Adimi, Parvin
AU - Jakobsen, Anders
AU - Dahl Steffensen, Karina
N1 - Publisher Copyright: © 2021 The Authors
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Circulating tumor DNA
KW - Droplet digital PCR
KW - HOXA9 methylation
KW - Ovarian cancer
KW - Sense-antisense
U2 - 10.1016/j.cca.2021.08.020
DO - 10.1016/j.cca.2021.08.020
M3 - Journal article
C2 - 34419462
AN - SCOPUS:85113677425
VL - 522
SP - 152
EP - 157
JO - Clinica Chimica Acta
JF - Clinica Chimica Acta
SN - 0009-8981
ER -
ID: 304061605