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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.
PMID
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Authors

Mayor MeshTerms

DNA Methylation

Keywords

C19MC microRNA

RASSF1A sequence

fetal DNA

gestational trophoblastic disease

screening

sex-determining region Y sequence

Journal Title tumour biology : the journal of the international society for oncodevelopmental biology and medicine
Publication Year Start




PMID- 28381180
OWN - NLM
STAT- MEDLINE
DA  - 20170406
DCOM- 20170418
LR  - 20170418
IS  - 1423-0380 (Electronic)
IS  - 1010-4283 (Linking)
VI  - 39
IP  - 4
DP  - 2017 Apr
TI  - Follow-up of gestational trophoblastic disease/neoplasia via quantification of
      circulating nucleic acids of placental origin using C19MC microRNAs,
      hypermethylated RASSF1A, and SRY sequences.
PG  - 1010428317697548
LID - 10.1177/1010428317697548 [doi]
AB  - 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.
FAU - Hromadnikova, Ilona
AU  - Hromadnikova I
AD  - 1 Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, 
      Charles University, Prague, Czech Republic.
FAU - Kotlabova, Katerina
AU  - Kotlabova K
AD  - 1 Department of Molecular Biology and Cell Pathology, Third Faculty of Medicine, 
      Charles University, Prague, Czech Republic.
FAU - Krofta, Ladislav
AU  - Krofta L
AD  - 2 Institute for the Care of the Mother and Child, Third Faculty of Medicine,
      Charles University, Prague, Czech Republic.
FAU - Hron, Filip
AU  - Hron F
AD  - 2 Institute for the Care of the Mother and Child, Third Faculty of Medicine,
      Charles University, Prague, Czech Republic.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Tumour Biol
JT  - Tumour biology : the journal of the International Society for Oncodevelopmental
      Biology and Medicine
JID - 8409922
RN  - 0 (Chorionic Gonadotropin)
RN  - 0 (MicroRNAs)
RN  - 0 (RASSF1 protein, human)
RN  - 0 (SRY protein, human)
RN  - 0 (Sex-Determining Region Y Protein)
RN  - 0 (Tumor Suppressor Proteins)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Adolescent
MH  - Adult
MH  - Chorionic Gonadotropin/blood
MH  - DNA/*blood
MH  - *DNA Methylation
MH  - Female
MH  - Follow-Up Studies
MH  - Gestational Trophoblastic Disease/blood/*diagnosis/genetics
MH  - Humans
MH  - MicroRNAs/*blood
MH  - Middle Aged
MH  - Pregnancy
MH  - Sex-Determining Region Y Protein/*genetics
MH  - Tumor Suppressor Proteins/*genetics
OTO - NOTNLM
OT  - C19MC microRNA
OT  - RASSF1A sequence
OT  - fetal DNA
OT  - gestational trophoblastic disease
OT  - screening
OT  - sex-determining region Y sequence
EDAT- 2017/04/07 06:00
MHDA- 2017/04/19 06:00
CRDT- 2017/04/07 06:00
AID - 10.1177/1010428317697548 [doi]
PST - ppublish
SO  - Tumour Biol. 2017 Apr;39(4):1010428317697548. doi: 10.1177/1010428317697548.

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