Expression profiles of tumour-suppressor miRNAs in endometrial cancer patients

Authors: Lenka Kalinková 1    Karol Kajo 1,2    Lenka Wachsmannová 1    Iveta Zmetáková 1    Ivana Fridrichová 1   
1 Cancer Research Institute, Biomedical Research Center of Slovak Academy of Sciences, Dúbravská cesta 9, 845 05 Bratislava, Slovakia    2 Pathology Institute, St. Elisabeth Cancer Institute, Heydukova 10, 812 50 Bratislava, Slovakia   
Year: 2020
Section: Cellular metabolism, physiology, molecular biology and genetics
Abstract No.: 1997
ISBN: 978-80-972360-6-9

Endometrial carcinoma (EC) belongs to the most common gynaecological malignancies with increasing incidence and mortality worldwide. Classification of EC represents two types, the endometrioid (EEC) (70-80% of all EC) and rarer serous histological type (ESC) (10-20%), However, EC with ambiguous morphology is problematic to classify. In cancers, the aberrant expression of microRNAs (miRNAs), small non-coding RNA molecules, was observed; therefore, it could represents a new biomarker for diagnosis, therapy prediction and prognosis of malignancies. The aim of this study was to investigate if the selected microRNA expression profiles could distinguish the morphologically defined EEC from ESC types and low- from high-grade EEC. We analyzed formalin fixed paraffin-embedded (FFPE) tumour tissue samples from 62 strictly characterized EC patients, 20 and 21 from EEC patients with Grade 1 and Grade 3 tumours, and 21 ESC, and 20 samples of non-malignant endometrium. miRNAs expression levels were analyzed by real-time PCR using miScript miRNA PCR Array Human Tumor Suppressor miRNAs (MIHS-119Z, Qiagen). When we compared expression of 84 tumor-suppressor miRNAs in well and poorly differentiated EEC and ESC to miRNA expression of control group, we found significantly differently expressed and deregulated 36 miRNAs at least in one of compared EEC group (Grade 1 and Grade 3) to controls and 35 miRNAs were detected in EEC (Grade1 + Grade 3) and ESC comparison to controls. Among them, we observed significantly downregulated four miRNAs, namely let-7c-5p, miR-125b-5p, miR-23b-3p and miR-99a-5p, in EEC Grade 3 in comparison to Grade 1 and we also found the significant differences in expression of another four miRNAs let-7g-5p, miR-195-5p, miR-34a-5p and miR-497-5p in ESC versus EEC. Our results showed that various EC histological types and well and poorly differentiated EEC are distinguished by different miRNA expression levels. These discriminating miRNAs could play some role in EC tumourigenesis and could serve as new biomarkers for more clear EC classification.

This work was supported by the Ministry of Health of the Slovak Republic under project registration number 2018/45-SAV-4.