Circulating cell-free DNA is elevated in postmenopausal compared with pre- and perimenopausal women.

Fisher, T; Powell, E; Yuwono, NL; Ford, CE; Warton, K

Circulating cell-free DNA is elevated in postmenopausal compared with pre- and perimenopausal women.

Fisher, T

Powell, E Yuwono, NL Ford, CE Warton, K

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Publisher:: Lippincott, Williams & Wilkins
Publication Type:: Journal Article
Citation:: Menopause, 2024, 31, (3), pp. 171-175
Issue Date:: 2024-03-01

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Field	Value	Language
dc.contributor.author	Fisher, T https://orcid.org/0000-0002-2298-0172
dc.contributor.author	Powell, E
dc.contributor.author	Yuwono, NL
dc.contributor.author	Ford, CE
dc.contributor.author	Warton, K
dc.date.accessioned	2025-02-12T21:58:39Z
dc.date.available	2025-02-12T21:58:39Z
dc.date.issued	2024-03-01
dc.identifier.citation	Menopause, 2024, 31, (3), pp. 171-175
dc.identifier.issn	1072-3714
dc.identifier.issn	1530-0374
dc.identifier.uri	http://hdl.handle.net/10453/185078
dc.description.abstract	OBJECTIVE: With the rising use of circulating cell-free DNA (cirDNA) liquid biopsies for disease screening, it is important to understand biological differences that may impact the accuracy of cirDNA-based clinical tests. Although a number of biological factors have been researched, the relationship between menopause and cirDNA has not been thoroughly investigated. We aimed to compare plasma cirDNA concentration and DNA fragment integrity in healthy women pre- and postmenopause. METHODS: Blood was collected from healthy female volunteers 40 years and older. cirDNA was extracted from plasma (n = 52) and quantified by quantitative polymerase chain reaction (n = 47; 26 premenopause, mean age-46 y; 21 postmenopause, mean age-59 y). cirDNA concentration was quantitated using an ALU repetitive sequence with a 115-base-pair (bp) product (ALU-115), and long cirDNA fragments were quantitated using an ALU repetitive sequence with a 247-bp product (ALU-247). cirDNA integrity was expressed as a ratio of ALU-247 over ALU-115. Mann-Whitney U test was used to compare pre- and postmenopause qPCR results, and a two-tailed, unpaired t test was undertaken to compare the integrity ratio between the two groups. RESULTS: Postmenopause plasma samples were found to have a significantly higher cirDNA concentration (P < 0.0001, premenopause: mean, 3.10 ± 1.84 ng/mL; median, 2.90 ng/mL; postmenopause: mean, 5.28 ± 2.76 ng/mL; median, 4.56 ng/mL) and significantly higher concentration of long-stranded cirDNA fragments (P = 0.0033, premenopause: mean, 1.06 ± 0.48 ng/mL; median, 0.96 ng/mL; postmenopause: mean, 1.69 ± 0.89 ng/mL; median, 1.48 ng/mL). There was no significant difference in the integrity ratio between the groups (P = 0.1788). CONCLUSIONS: Plasma cirDNA concentrations are higher in postmenopausal women. This has important implications in cirDNA liquid biopsy development and screening, especially for diseases such as cancer where the majority of cases are diagnosed postmenopause.
dc.format	Print
dc.language	eng
dc.publisher	Lippincott, Williams & Wilkins
dc.relation.ispartof	Menopause
dc.relation.isbasedon	10.1097/GME.0000000000002313
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	11 Medical and Health Sciences
dc.subject.classification	Obstetrics & Reproductive Medicine
dc.subject.classification	32 Biomedical and clinical sciences
dc.subject.classification	42 Health sciences
dc.subject.classification	52 Psychology
dc.subject.mesh	Cell-Free Nucleic Acids
dc.subject.mesh	DNA
dc.subject.mesh	Female
dc.subject.mesh	Humans
dc.subject.mesh	Middle Aged
dc.subject.mesh	Perimenopause
dc.subject.mesh	Postmenopause
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Middle Aged
dc.subject.mesh	Postmenopause
dc.subject.mesh	Perimenopause
dc.subject.mesh	DNA
dc.subject.mesh	Cell-Free Nucleic Acids
dc.subject.mesh	Humans
dc.subject.mesh	DNA
dc.subject.mesh	Perimenopause
dc.subject.mesh	Postmenopause
dc.subject.mesh	Middle Aged
dc.subject.mesh	Female
dc.subject.mesh	Cell-Free Nucleic Acids
dc.subject.mesh	Humans
dc.subject.mesh	Female
dc.subject.mesh	Middle Aged
dc.subject.mesh	Postmenopause
dc.subject.mesh	Perimenopause
dc.subject.mesh	DNA
dc.subject.mesh	Cell-Free Nucleic Acids
dc.title	Circulating cell-free DNA is elevated in postmenopausal compared with pre- and perimenopausal women.
dc.type	Journal Article
utslib.citation.volume	31
utslib.location.activity	United States
utslib.for	11 Medical and Health Sciences
pubs.organisational-group	University of Technology Sydney
pubs.organisational-group	University of Technology Sydney/Faculty of Science
pubs.organisational-group	University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access	*
pubs.consider-herdc	false
dc.rights.license	This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License (CC BY-NC-ND 4.0). To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.date.updated	2025-02-12T21:58:37Z
pubs.issue	3
pubs.publication-status	Published
pubs.volume	31
utslib.citation.issue	3

Abstract:

OBJECTIVE: With the rising use of circulating cell-free DNA (cirDNA) liquid biopsies for disease screening, it is important to understand biological differences that may impact the accuracy of cirDNA-based clinical tests. Although a number of biological factors have been researched, the relationship between menopause and cirDNA has not been thoroughly investigated. We aimed to compare plasma cirDNA concentration and DNA fragment integrity in healthy women pre- and postmenopause. METHODS: Blood was collected from healthy female volunteers 40 years and older. cirDNA was extracted from plasma (n = 52) and quantified by quantitative polymerase chain reaction (n = 47; 26 premenopause, mean age-46 y; 21 postmenopause, mean age-59 y). cirDNA concentration was quantitated using an ALU repetitive sequence with a 115-base-pair (bp) product (ALU-115), and long cirDNA fragments were quantitated using an ALU repetitive sequence with a 247-bp product (ALU-247). cirDNA integrity was expressed as a ratio of ALU-247 over ALU-115. Mann-Whitney U test was used to compare pre- and postmenopause qPCR results, and a two-tailed, unpaired t test was undertaken to compare the integrity ratio between the two groups. RESULTS: Postmenopause plasma samples were found to have a significantly higher cirDNA concentration (P < 0.0001, premenopause: mean, 3.10 ± 1.84 ng/mL; median, 2.90 ng/mL; postmenopause: mean, 5.28 ± 2.76 ng/mL; median, 4.56 ng/mL) and significantly higher concentration of long-stranded cirDNA fragments (P = 0.0033, premenopause: mean, 1.06 ± 0.48 ng/mL; median, 0.96 ng/mL; postmenopause: mean, 1.69 ± 0.89 ng/mL; median, 1.48 ng/mL). There was no significant difference in the integrity ratio between the groups (P = 0.1788). CONCLUSIONS: Plasma cirDNA concentrations are higher in postmenopausal women. This has important implications in cirDNA liquid biopsy development and screening, especially for diseases such as cancer where the majority of cases are diagnosed postmenopause.

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http://hdl.handle.net/10453/185078