title: Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated RASSF1A, and SRY sequences.
abstract: The aim of the study was to evaluate the effectiveness of placental-specific markers, extracellular fetal DNA (sex-determining region Y and hypermethylated RASSF1A sequences) and circulating C19MC microRNAs (miR-516-5p, miR-517-5p, miR-518b, miR-520a-5p, miR-520h, miR-525, and miR-526a) for the diagnosis and consecutive follow-up of gestational trophoblastic disease/neoplasia. Increased levels of extracellular fetal DNA and C19MC microRNAs were detected in patients with active disease when compared with the period when the patients reached remission of the disease. The positive correlation between plasma levels of hypermethylated RASSF1A sequence, C19MC microRNAs, and human chorionic gonadotropin serum levels was found. MiR-520a-5p had the best performance to detect patients with active disease (a positive predictive value of 100% at a null false positive ratio (FPR)). MiR-516-5p and miR-525 were able to diagnose 100% of women with active disease at the FPR 3.9%/7.7%. The overall predictive capacity of single miR-526a (81.8% at null FPR), miR-517-5p (90.9% at 15.4% FPR), miR-518b (100% at 38.5% FPR), and miR-520h (90.9% at 26.9% FPR) biomarkers to detect active disease cases was slightly lower. Transient increase in C19MC microRNA plasma levels after the first cycle of chemotherapy indicated the decay of placental trophoblast residual tissue. The increased levels of extracellular fetal DNA and placental-specific C19MC microRNAs are associated with gestational trophoblastic disease/neoplasia. Screening of extracellular placental-specific biomarkers may represent an additional option to identify a significant proportion of women with active disease and to monitor the therapy response. Non-invasive follow-up of the decomposing residual tissue in the form of extracellular nucleic acids of placental origin packed into apoptotic bodies derived from placental trophoblasts is available.
authors.affiliation: 1 Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Ilona
authors.initials: I
authors.lastname: Hromadnikova
authors.affiliation: 1 Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Katerina
authors.initials: K
authors.lastname: Kotlabova
authors.affiliation: 2 Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Ladislav
authors.initials: L
authors.lastname: Krofta
authors.affiliation: 2 Institute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech Republic.
authors.forename: Filip
authors.initials: F
authors.lastname: Hron
mesh_terms: D000293:Adolescent; D000328:Adult; D006063:Chorionic Gonadotropin / Q000097:blood; D004247:DNA / Q000097:blood*; D019175:DNA Methylation; D005260:Female; D005500:Follow-Up Studies; D031901:Gestational Trophoblastic Disease / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D035683:MicroRNAs / Q000097:blood*; D008875:Middle Aged; D011247:Pregnancy; D051876:Sex-Determining Region Y Protein / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: D006063:Chorionic Gonadotropin; D035683:MicroRNAs; C411762:RASSF1 protein, human; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; D025521:Tumor Suppressor Proteins; D004247:DNA
keywords: C19MC microRNA; RASSF1A sequence; fetal DNA; gestational trophoblastic disease; screening; sex-determining region Y sequence