Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated , and sequences

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 diag...

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Main Authors: Ilona Hromadnikova, Katerina Kotlabova, Ladislav Krofta, Filip Hron
Format: Article
Language:English
Published: SAGE Publishing 2017-04-01
Series:Tumor Biology
Online Access:https://doi.org/10.1177/1010428317697548
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author Ilona Hromadnikova
Katerina Kotlabova
Ladislav Krofta
Filip Hron
author_facet Ilona Hromadnikova
Katerina Kotlabova
Ladislav Krofta
Filip Hron
author_sort Ilona Hromadnikova
collection DOAJ
description 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.
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spelling doaj-art-76ca74d9762f45dc91e2ffe931c117c82025-08-20T03:33:45ZengSAGE PublishingTumor Biology1423-03802017-04-013910.1177/1010428317697548Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated , and sequencesIlona Hromadnikova0Katerina Kotlabova1Ladislav Krofta2Filip Hron3Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech RepublicDepartment of Molecular Biology and Cell Pathology, Third Faculty of Medicine, Charles University, Prague, Czech RepublicInstitute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech RepublicInstitute for the Care of the Mother and Child, Third Faculty of Medicine, Charles University, Prague, Czech RepublicThe 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.https://doi.org/10.1177/1010428317697548
spellingShingle Ilona Hromadnikova
Katerina Kotlabova
Ladislav Krofta
Filip Hron
Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated , and sequences
Tumor Biology
title Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated , and sequences
title_full Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated , and sequences
title_fullStr Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated , and sequences
title_full_unstemmed Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated , and sequences
title_short Follow-up of gestational trophoblastic disease/neoplasia via quantification of circulating nucleic acids of placental origin using C19MC microRNAs, hypermethylated , and sequences
title_sort follow up of gestational trophoblastic disease neoplasia via quantification of circulating nucleic acids of placental origin using c19mc micrornas hypermethylated and sequences
url https://doi.org/10.1177/1010428317697548
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