Elsevier

Placenta

Volume 35, Issue 9, September 2014, Pages 787-789
Placenta

Short communication
Clinical applications of analysis of plasma circulating complete hydatidiform mole pregnancy-associated miRNAs in gestational trophoblastic neoplasia: A preliminary investigation

https://doi.org/10.1016/j.placenta.2014.06.004Get rights and content

Highlights

  • Plasma CHM-miRNA analysis could be used as an additional follow-up test for GTN.

  • Plasma CHM-miRNA test may avoid false-positive/negative results of hCG immunoassay.

  • Altered levels of plasma CHM-miRNAs may reflect MTX-induced apoptotic activity.

  • Plasma CHM-miRNA test provides different information to hCG immunoassay.

Abstract

The aim of this study was to investigate the clinical application of plasma complete hydatidiform mole pregnancy-associated microRNAs (CHM-miRNAs: hsa-miR-520b, hsa-miR-520f and hsa-miR-520c-3p). We measured plasma CHM-miRNA concentration by real-time quantitative reverse transcriptase polymerase chain reaction in two cases of CHM resulting in gestational trophoblastic neoplasia later. As progress of treatments in both cases, the plasma concentrations of CHM-miRNAs showed a decreasing tendency similar to the pattern for serum hCG concentration, but exhibited a transient increasing tendency after each course of chemotherapy, suggesting that the plasma CHM-miRNAs could be an additional follow-up marker for malignant changes of CHM.

Introduction

Complete hydatidiform mole (CHM) pregnancy-associated miRNAs (CHM-miRNAs; hsa-miR-520b, hsa-miR-520f and hsa-miR-520c-3p) were recently identified in the plasma [1]. The measurement of CHM-miRNAs may be used in clinical management of CHM as a follow-up molecular marker, in addition to the current biochemical marker human chorionic gonadotropin (hCG), which has α- and β-subunits. Malignant change, termed gestational trophoblastic neoplasia (GTN), arises after 15% of cases of CHM pregnancy [2]. Onset of malignant change is signified by a plateaued or rising hCG concentration. However, because GTN generates many other subtypes of hCG, hCG immunoassays fail to or variably detect all hCG variants (e.g. regular hCG, hyperglycosylated hCG and the free beta-subunit of hyperglycosylated hCG, etc.) [3], and therefore are prone to false-negative results [4], [5]. Additionally, hCG assays are susceptible to false-positive results, e.g. phantom hCG that is a physiological entity, analytical problem caused by crossreacting heterophilic antibodies [4], [5], [6]. Therefore, a new generation of assays for GTN is urgently needed.

In this study, we measured plasma CHM-miRNAs (hsa-miR-520b, hsa-miR-520f and hsa-miR-520c-3p) concentration by real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in two cases of CHM resulting in GTN later.

Section snippets

Sample collection

Two cases of CHM resulting in GTN later were analyzed in this study. CHM was diagnosed by pathological, chromosomal and DNA genotyping tests. Serial blood sampling was performed at times, before and after suction evacuation or chemotherapy. Preparation and extraction of total RNA containing small RNA molecules were performed as described previously [7], [8].

Real-time quantitative reverse-transcription polymerase chain reaction (qRT-PCR) analysis

All specific primers and TaqMan probes (hsa-miR-520b, hsa-miR-520f and hsa-miR-520c-3p) were purchased from TaqMan MicroRNA Assays (Applied

Results and discussion

The first case was a 32-year-old woman with Stage I GTN, which was diagnosed by the International Federation of Gynecology and Obstetrics (FIGO) 2000 staging. In this case, initial chest X-ray indicated no pulmonary lesions, and the first and second evacuations were performed on Days 0 and 7, respectively (Fig. 1A). Serum hCG levels (300, 300 mIU/mL on Day 0) fell to 279 mIU/mL up to Day 38 (Fig. 1A). However, re-elevation of the hCG levels was detected from Day 50 (1004 mIU/mL) to Day 76

Authors' contribution

All authors confirm that they have contributed to the intellectual content of this paper and have met the following requirements: (1): significant contributions to the conception and design, acquisition of data, or analysis and interpretation of data; (2) drafting or revising the article for intellectual content; and (3) final approval of the published article.

Funding

This work was supported by the Japan Society for the Promotion of Science KAKENHI grant numbers nos. 26462495, 24791712 and 25462563.

Acknowledgments

We would like to thank Dr. Atsushi Yoshida for their technical assistance.

References (9)

There are more references available in the full text version of this article.

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