卵巢癌
肿瘤科
医学
癌症
DNA甲基化
内科学
胎儿游离DNA
前瞻性队列研究
妇科
生物
怀孕
基因
产前诊断
遗传学
基因表达
胎儿
作者
Chiara Herzog,Allison Jones,Iona Evans,Daniel Reisel,Adeola Olaitan,Konstantinos Doufekas,Nicola MacDonald,Angelique Flöter Rådestad,Kristina Gemzell‐Danielsson,Michal Zikán,David Cibula,Lukáš Dostálek,Tobias Paprotka,Andreas Leimbach,Mark R. Schmitt,Andy Ryan,Aleksandra Gentry‐Maharaj,Sophia Apostolidou,Adam N. Rosenthal,Usha Menon,Martin Widschwendter
摘要
Abstract Analysis of cell‐free DNA methylation (cfDNAme), alone or combined with CA125, could help to detect ovarian cancers earlier and may reduce mortality. We assessed cfDNAme in regions of ZNF154, C2CD4D and WNT6 via targeted bisulfite sequencing in diagnostic and early detection (preceding diagnosis) settings. Diagnostic samples were obtained via prospective blood collection in cell‐free DNA tubes in a convenience series of patients with a pelvic mass. Early detection samples were matched case‐control samples derived from the UK Familial Ovarian Cancer Screening Study (UKFOCSS). In the diagnostic set (n cases = 27, n controls = 41), the specificity of cfDNAme was 97.6% (95% CI: 87.1%‐99.9%). High‐risk cancers were detected with a sensitivity of 80% (56.3%‐94.3%). Combination of cfDNAme and CA125 resulted in a sensitivity of 94.4% (72.7%‐99.9%) for high‐risk cancers. Despite technical issues in the early detection set (n cases = 29, n controls = 29), the specificity of cfDNAme was 100% (88.1%‐100.0%). We detected 27.3% (6.0%‐61.0%) of high‐risk cases with relatively lower genomic DNA (gDNA) contamination. The sensitivity rose to 33.3% (7.5%‐70.1%) in samples taken <1 year before diagnosis. We detected ovarian cancer in several patients up to 1 year before diagnosis despite technical limitations associated with archival samples (UKFOCSS). Combined cfDNAme and CA125 assessment may improve ovarian cancer screening in high‐risk populations, but future large‐scale prospective studies will be required to validate current findings.
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