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Clin Epigenetics. 2017 Jul 21;9:72. doi: 10.1186/s13148-017-0372-0. eCollection 2017.

MicroRNA profiling of ovarian granulosa cell tumours reveals novel diagnostic and prognostic markers.

Author information

1
Department of Obstetrics and Gynaecology, The University of Auckland, Auckland, New Zealand.
2
Centre for Reproductive Health, Queen's Medical Research Institute, University of Edinburgh, Edinburgh, UK.
3
Department of Medical Oncology, Auckland City Hospital, Auckland, New Zealand.
4
Department of Pathology, Auckland City Hospital, Auckland, New Zealand.
5
Department of Molecular Medicine and Pathology, The University of Auckland, Private Bag 92019, Auckland Mail Centre, Auckland, 1142 New Zealand.
6
School of Biological Sciences, The University of Auckland, Auckland, New Zealand.
#
Contributed equally

Abstract

BACKGROUND:

The aim of this study was to explore the clinical utility of microRNAs (miRNAs) as improved markers of ovarian granulosa cell tumours (GCTs) for cancer diagnosis and prognosis prediction. Current histopathological and genetic markers, such as the presence of a FOXL2 gene mutation to distinguish between the two major subtypes are not wholly accurate and as such novel biomarkers are warranted.

METHODS:

The miRNA expression profiles of five formalin-fixed, paraffin-embedded (FFPE) adult-GCTs and five juvenile-GCTs were assessed using Affymetrix miRNA 3.0 Arrays and compared for differential expression. Ten miRNAs were assessed in an additional 33 FFPE tumours and four normal granulosa cell samples by quantitative RT-PCR, and their expression correlated to clinical information.

RESULTS:

MicroRNA array found 37 miRNAs as differentially expressed between the two GCT subtypes (p < 0.05, fold change ≥2 and among these, miRs -138-5p, -184, -204-5p, -29c-3p, -328-3p and -501-3p were validated by RT-qPCR as differentially expressed between the two GCT subtypes (p < 0.05). In addition, the expression of miR-184 was predictive of tumour recurrence in adult-GCTs, specifically for patients diagnosed with stage I and II and stage I only disease (p < 0.001 and p < 0.05, respectively).

CONCLUSIONS:

This study is the first to report on global miRNA expression profiles of human ovarian GCTs using FFPE tumour samples. We have validated six miRNAs as novel markers for subtype classification in GCTs with low levels of miR-138-5p correlating with early tumour stage. Low miR-184 abundance was correlated with tumour recurrence in early stage adult-GCT patients as a candidate predictive biomarker. Further studies are now needed to confirm the clinical utility of these miRNAs as diagnostic and recurrence markers, and understand their possible roles in the pathogenesis of GCTs.

KEYWORDS:

Granulosa cell; Non-coding RNA; Ovarian cancer; Prognosticator; Tissue biomarker

PMID:
28736583
PMCID:
PMC5521084
DOI:
10.1186/s13148-017-0372-0
[Indexed for MEDLINE]
Free PMC Article

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