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. 2023 Dec 14;24(24):17470.
doi: 10.3390/ijms242417470.

miRNA Expression Profiles in Ovarian Endometriosis and Two Types of Ovarian Cancer-Endometriosis-Associated Ovarian Cancer and High-Grade Ovarian Cancer

Affiliations

miRNA Expression Profiles in Ovarian Endometriosis and Two Types of Ovarian Cancer-Endometriosis-Associated Ovarian Cancer and High-Grade Ovarian Cancer

Maria Szubert et al. Int J Mol Sci. .

Abstract

Endometriosis-associated ovarian cancer (EOC) consisting of endometrioid cancer and clear-cell ovarian cancer could be promoted by many factors. miRNAs, which are small, non-coding molecules of RNA, are among them. The aim of this study was to detect miRNAs connected with the malignant transformation of endometriosis. FFPE (formalin-fixed, paraffin-embedded) samples of 135 patients operated on for endometriosis and different types of ovarian cancer (EOC and HGSOC-high-grade serous ovarian cancer) were studied. Healthy ovarian tissue was used as a control group. From the expression panel of 754 miRNAs, 7 were chosen for further tests according to their ROC (receiver operating characteristic) curves: miR-1-3p, miR-125b-1-3p, miR-31-3p, miR-200b-3p, miR-502-5p, miR-503-5p and miR-548d-5p. Furthermore, other potentially important clinical data were analysed, which included age, BMI, Ca-125 concentration, miscarriages and deliveries and concomitant diseases such as hypertension, type 2 diabetes and smoking. Among the miRNAs, miR200b-3p had the lowest expression in neoplastic tissues. miR31-3p had the highest expression in women without any lesions in the ovaries. miR-502-5p and miR-548-5p did not differ between the studied groups. The examined miRNA panel generally distinguished significantly normal ovarian tissue and endometriosis, normal ovarian tissue and cancer, and endometriosis and cancer. The malignant transformation of endometriosis is dependent on different factors. miRNA changes are among them. The studied miRNA panel described well the differences between endometriosis and EOC but had no potential to differentiate types of ovarian cancer according to their origin. Therefore, examination of a broader miRNA panel is needed and might prove itself advantageous in clinical practice.

Keywords: carcinogenesis; endometrial cyst; endometriosis; miRNA; ovarian cancer.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study, in the collection, analyses, or interpretation of data, in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
miR-502-5p (A) and miR-548-5p (B) expression in studied groups (ANOVA test). p-values between each group written above the box-plots. Y-axis shows Relative Quantification (RQ) value (Δ Δ CT) to reference gene miR-191-5p. EOC—endometriosis-associated ovarian cancer; HGSOC—high-grade ovarian cancer; EC—endometrial cyst; CG—control group. The remaining microRNAs showed differential expression between groups (Table 3), which we further explain in Figure 2, Figure 3 and Figure 4.
Figure 2
Figure 2
Heatmap of the Relative Quantification of investigated miRNAs.
Figure 3
Figure 3
miRNAs with significantly altered expression between endometriosis-associated ovarian cancer (EOC) and ovarian endometriosis (EC) (ANOVA test with post hoc t-test). p-Values between each group written above the box-plots. Y-axis shows Relative Quantification (RQ) value (Δ Δ CT) to reference gene miR-191-5p. EOC—endometriosis-associated ovarian cancer, HGSOC—high-grade ovarian cancer, EC—endometrial cyst, CG—control group; (A)–miR-125-b-1-3p; (B)–miR-200b-3p; (C)–miR-31-3p.
Figure 4
Figure 4
(A) miR-1-3p significantly distinguished only benign and malignant tissue; miR-503-5p (B) had a lower expression in ovarian endometriosis than in all types of cancer (ANOVA test with post hoc t-test). p-Values between each group written above the box-plots. Y-axis shows Relative Quantification (RQ) value (Δ Δ CT) to reference gene miR-191-5p. EOC—endometriosis-associated ovarian cancer, HGSOC—high-grade ovarian cancer, EC—endometrial cyst, CG—control group.
Figure 5
Figure 5
The heatmap of connections between studied miRNAs and the most significant pathways (rows—subcategories of possible pathways, displayed in log base; columns—the studied miRNAs).

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Grants and funding

The project was supported by a scientific grant for the young scientist (Roche) from the Medical University of Lodz under number 570/1-004-01/570-01-082. There was no involvement of the sponsor in any part of the study or publishing process.