Abstract

Modern diagnostics are based on molecular analysis and have been focused on searching for new molecular markers to use in diagnostics. Included in this has been the search for the correlation between gene expression in tissue samples and liquid biological materials. The aim of this study was to evaluate the differences in the expression profile of messenger RNA (mRNA) and micro-RNA (miRNA) related to the epithelial–mesenchymal transition (EMT) in different grades of endometrial cancer (G1–G3), in order to select the most promising molecular markers. The study material consisted of tissue samples and whole blood collected from 30 patients with endometrial cancer (study group; G1 = 15; G2 = 8; G3 = 7) and 30 without neoplastic changes (control group). The molecular analysis included the use of the microarray technique and RTqPCR. Microarray analysis indicated the following number of mRNA differentiating the endometrial cancer samples from the control (tissue/blood): G1 vs. C = 21/18 mRNAs, G2 vs. C = 19/14 mRNAs, and G3 vs. C = 10/9 mRNAs. The common genes for the tissue and blood samples (Fold Change; FC > 3.0) were G1 vs. C: TGFB1, WNT5A, TGFB2, and NOTCH1; G2 vs. C: BCL2L, SOX9, BAMBI, and SMAD4; G3 vs. C STAT1 and TGFB1. In addition, mRNA TGFB1, NOTCH1, and BCL2L are common for all grades of endometrial cancer. The analysis showed that miR-144, miR-106a, and miR-30d are most strongly associated with EMT, making them potential diagnostic markers.

Highlights

  • An epithelial–mesenchymal transition (EMT) is a molecular and phenotypic process of reprogramming polarized and immobile epithelial cells into mobile mesenchymal cells, the consequence of which is an increase in mobility and invasion [1,2]

  • If the value of Fold Change (FC) is higher than 1.0, it means, compared to the control culture, that there is an overexpression of genes, whereas, if the FC value is lower than 1.0, compared to the control, there is a downregulation of genes

  • The following stage of molecular analysis was the assessment of the miRNA transcriptome in endometrial cancer samples and in whole blood obtained from oncological patients, compared to a control

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Summary

Introduction

An epithelial–mesenchymal transition (EMT) is a molecular and phenotypic process of reprogramming polarized and immobile epithelial cells into mobile mesenchymal cells, the consequence of which is an increase in mobility and invasion [1,2] During this process, it is observed, among other things, that there is a decrease in the expression of proteins, which strengthen the adherence of cells to one another, such as E-cadherin and γ-catenin, as well as an increase in the expression of mesenchymal markers (vimentin, N-cadherin, and fibronectin) and an increase in the activity of certain extracellular matrix metalloproteinases [3,4]. The initiation of EMT is essential so that the named processes can occur [7,8]

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