Background: Endometrial cancer (EC) is the most common malignant tumour of the uterus and is one of the most frequently diagnosed gynaecological cancers in developed countries. There has been an increase in mortality from endometrial cancer, which highlights the importance of a better understanding of the molecular mechanisms underlying its development and progression. MicroRNAs are responsible for post-transcriptional gene regulation; it has been shown that miR-222-3p and miR-21-5p target PTEN gene in many cancer types.
Objectives: The objective of the present study was to evaluate the expression level of the PTEN gene, miR-222-3p, and miR-21-5p in endometrial cancer tissue samples and assess their association with histological grade. Additionally, relationships between the expression of analysed microRNAs and the expression of their target - PTEN gene was assessed.
Methods: The study comprised of 89 patients with endometrial cancer. The control group included 19 subjects, while the endometrial intraepithelial neoplasia (EIN) group comprised 22 patients. Among patients with endometrial cancer, 30 were G1, 47 were G2, and 12 were G3. The analysis of PTEN gene expression was conducted using quantitative PCR (qPCR) with TaqMan probes. The expression levels of microRNAs were determined by digital PCR, a method that enables absolute quantification of microRNA copies.
Results: Analysis of PTEN gene expression revealed differences in expression levels between the groups studied (p<0.001). The lowest values of PTEN expression were observed in the G2 (1.17±0.61) and G3 (1.01±0.59) groups, while the highest levels were detected in the EIN group (1.93±0.86) and in tumours with low histological grade G1 (1.86±0.62). In the control group, the level of PTEN expression was 1.31±0.76. The expression of miR-222-3p exhibited a downward trend with the escalation of the histological grade of EC (p=0.0396). Statistical analysis revealed a marked decrease in expression of miR-222-3p in the G3 group in comparison to the control group. Conversely, the expression levels of miR-21-5p, no statistically significant differences were found between any of the compared groups (p=0.512), despite the observed quantitative differences. No correlation was observed between PTEN gene expression and the expression of the microRNAs studied.
Conclusions: The results indicate a gradual decrease in PTEN expression with increasing histological grade of endometrial cancer, thereby confirming the involvement of PTEN in tumour progression. Decreased PTEN expression in G2 and G3 grades suggests that tumour suppressor function is not maintained in the late stages of the disease. The reduced expression of miR-222-3p in the G3 group relative to the control group might be associated with an aggressive tumour phenotype. The expression of miR-21-5p did not demonstrate significant differentiation between the studied groups, which limits its significance as a biomarker of histological advancement. The absence of correlation between PTEN expression and the microRNAs studied suggests the presence of a other regulatory mechanisms for this gene in endometrial cancer.