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miRNA expression profiling in formalin-fixed paraffin-embedded endometriosis and ovarian cancer samples

Authors Braicu OL, Budisan L, Buiga R, Jurj A, Achimas-Cadariu P, Pop LA, Braicu C, Irimie A, Berindan-Neagoe I

Received 15 March 2017

Accepted for publication 31 May 2017

Published 28 August 2017 Volume 2017:10 Pages 4225—4238

DOI https://doi.org/10.2147/OTT.S137107

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Akshita Wason

Peer reviewer comments 3

Editor who approved publication: Dr William Cho

Ovidiu-Leonard Braicu,1 Liviuta Budisan,2 Rares Buiga,2,3 Ancuta Jurj,2 Patriciu Achimas-Cadariu,1,4 Laura Ancuta Pop,2 Cornelia Braicu,2 Alexandru Irimie,1,4 Ioana Berindan-Neagoe2,5,6

1Department of Surgery, Iuliu Hatieganu University of Medicine and Pharmacy, Cluj-Napoca, 2Research Center for Functional Genomics, Biomedicine and Translational Medicine, Iuliu Hatieganu University of Medicine and Pharmacy, 3Pathology Department, The Oncology Institute Prof. Dr. Ion Chiricuta, Cluj-Napoca, 4Department of Surgical Oncology, The Oncology Institute Prof. Dr. Ion Chiricuta, Cluj-Napoca, 5MEDFUTURE-Research Center for Advanced Medicine, University of Medicine and Pharmacy Iuliu-Hatieganu, Cluj-Napoca, 6Department of Functional Genomics, Proteomics and Experimental Pathology, The Oncology Institute Prof. Dr. Ion Chiricuta, Cluj-Napoca, Romania

Abstract: Endometriosis is an inflammatory pathology associated with a negative effect on life quality. Recently, this pathology was connected to ovarian cancer, in particular with endometrioid ovarian cancer. microRNAs (miRNAs) are a class of RNA transcripts ~19–22 nucleotides in length, the altered miRNA pattern being connected to pathological status. miRNAs are highly stable transcripts, and these can be assessed from formalin-fixed paraffin-embedded (FFPE) samples leading to the identification of miRNAs that could be developed as diagnostic and prognostic biomarkers, in particular those involved in malignant transformation. The aim of our study was to evaluate miRNA expression pattern in FFPE samples from endometriosis and ovarian cancer patients using PCR-array technology and also to compare the differential expression pattern in ovarian cancer versus endometriosis. For the PCR-array study, we have used nine macrodissected FFPE samples from endometriosis tissue, eight samples of ovarian cancers and five normal ovarian tissues. Quantitative real-time PCR (qRT-PCR) was used for data validation in a new patient cohort of 17 normal samples, 33 endometriosis samples and 28 ovarian cancer macrodissected FFPE samples. Considering 1.5-fold expression difference as a cut-off level and a P-value <0.05, we have identified four miRNAs being overexpressed in endometrial tissue, while in ovarian cancer 15 were differentially expressed (nine overexpressed and six downregulated). The expression level was confirmed by qRT-PCR for miR-93, miR-141, miR-155, miR-429, miR-200c, miR-205 and miR-492. Using the interpretative program Ingenuity Pathway Analysis revealed several deregulated pathways due to abnormal miRNA expression in endometriosis and ovarian cancer, which in turn is responsible for pathogenesis; this differential expression of miRNAs can be exploited as a therapeutic target. A higher number of altered miRNAs were detected in endometriosis versus ovarian cancer tissue, most of them being linked with epithelial-to-mesenchymal transition.

Keywords: endometriosis, ovarian cancer, miRNA, formalin-fixed paraffin-embedded samples

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