Małgorzata Tokłowicz

Hsa-miR-21-5p and Hsa-miR-145-5p Expression: From Normal Tissue to Malignant Changes—Context-Dependent Correlation with Estrogen- and Hypoxia–Vascularization-Related Pathways Genes: A Pilot Study

Ovarian cancer (OC) is a severe gynecological malignancy with a high mortality rate among women worldwide. It is often diagnosed at advanced stages due to the lack of effective screening methods. This study investigated the expression patterns of microRNAs (miRNAs) hsa-miR-21-5p and hsa-miR-145-5p as potential OC prognostic and diagnostic biomarkers and their correlation with estrogen-dependent (ESR1 & 2, PELP1 and c-SRC) and hypoxia–neovascularization-induced (HIF1A, EPAS1, and VEGFA) pathway genes. Tissue samples obtained from twenty patients with confirmed ovarian cancer and twenty controls were analyzed using quantitative polymerase chain reaction (qPCR) to examine miRNA and mRNA levels. The qPCR analysis revealed significantly higher hsa-miR-21-5p and lower hsa-miR-145-5p expression in OC tissues than controls. Moreover, a significant trend was observed in hsa-miR-21-5p and hsa-miR-145-5p expression levels across normal, non-cancerous changes and malignant ovarian tissues. The hsa-miR-21-5p showed better diagnostic potential than hsa-miR-145-5p. We also observed inconsistent correlations in hsa-miR-21-5p and hsa-mir-145-5p and estrogen-related and hypoxia–neovascularization-dependent genes in ovarian cancer across all groups. This suggests that the relationship between these miRNAs and the selected genes is context-specific. Our findings suggest that hsa-miR-21-5p and hsa-miR-145-5p expression levels may be prognostic or diagnostic markers for ovarian cancer patients.

HIF1A, EPAS1, and VEGFA: angiogenesis and hypoxia-related gene expression in endometrium and endometrial epithelial tumors

Abstract Endometrial cancer (EC) is the second most frequent gynecological malignancy and the sixth most common women’s cancer worldwide. EC incidence rate is increasing rapidly. Apart from the classical, we should consider angiogenesis and hypoxia-related genes as a reason for EC manifestation and progression. We compared the patterns of HIF1A , EPAS1 , and VEGFA (genes of interest – GOIs) mRNA expression in 92 cases. HIF1A and VEGFA levels were higher in EC patients than in controls. VEGFA differed significantly between controls and both tumor grades G2 and G3, and we observed a positive correlation for HIF1A and VEGFA with EC grading. VEGFA levels were significantly higher in post-menopausal compared to pre-menopausal patients. All GOIs demonstrated strong correlations in pre-menopausal cases and weak correlations in post-menopausal cases. A positive correlation was observed in pre-menopausal controls for all GOIs and in post-menopausal patients for only EPAS1 and VEGFA . HIF1A and EPAS1 positively correlated with VEGFA in post-menopausal EC cases. Multiple linear regression analyses revealed that menopause, body mass index (BMI), and HIF1A expression are significant stimulating factors for EC occurrence. HIF1A levels were higher in EC patients after BMI and comorbidity number adjustment. The gene-to-gene relation could be seen as either a diagnostic or a therapeutic target in EC. Physicians should inform patients about modifiable risk factors such as BMI. Second, more attention should be paid to diagnosing patients with comorbidities in older age and after menopause. These factors should be considered in designing angiogenesis and hypoxia-related gene-targeting therapies.

Altered Expression of ESR1, ESR2, PELP1 and c-SRC Genes Is Associated with Ovarian Cancer Manifestation

Ovarian cancer remains the leading cause of death due to gynecologic malignancy. Estrogen-related pathways genes, such as estrogen receptors (ESR1 and ESR2) and their coregulators, proline-, glutamic acid-, and leucine-rich protein 1 (PELP1), and proto-oncogene tyrosine-protein kinase c-Src (SRC) are involved in ovarian cancer induction and development, still they require in-depth study. In our study, tissue samples were obtained from 52 females of Caucasian descent (control group without cancerous evidence (n = 27), including noncancerous benign changes (n = 15), and the ovarian carcinoma (n = 25)). Using quantitative analyses, we investigated ESRs, PELP1, and SRC mRNA expression association with ovarian tumorigenesis. Proteins’ presence and their location were determined by Western blot and immunohistochemistry. Results showed that PELP1 and SRC expression levels were found to differ in tissues of different sample types. The expression patterns were complex and differed in the case of ovarian cancer patients compared to controls. The most robust protein immunoreactivity was observed for PELP1 and the weakest for ESR1. The expression patterns of analyzed genes represent a potentially interesting target in ovarian cancer biology, especially PELP1. This study suggests that specific estrogen-mediated functions in the ovary and ovary-derived cancer might result from different local interactions of estrogen with their receptors and coregulators.