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. 2025 Jan 31.
doi: 10.1007/s13353-025-00939-7. Online ahead of print.

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

Monika Englert-Golon  1 , Małgorzata Tokłowicz #  2 , Aleksandra Żbikowska #  2 , Stefan Sajdak  3   4 , Małgorzata Kotwicka  2 , Paweł Jagodziński  5 , Andrzej Pławski  6 , Mirosław Andrusiewicz  7
Affiliations

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

Monika Englert-Golon et al. J Appl Genet. .

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.

Keywords: Endometrial cancer (EC); Hypoxia-inducible factor 1A gene (HIF1A); Hypoxia-inducible factor 2A/endothelial PAS domain protein 1 gene (HIF2A/EPAS1); Hypoxia-inducible factors (HIFs); Vascular endothelial growth factor A gene (VEGFA).

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Conflict of interest statement

Declarations. Institutional review board statement: The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the Institutional Review Board of Poznan University of Medical Sciences (protocol code Nos. 593/19 and 594/19 date of approval 6/19/2019). Informed consent: Written informed consent was obtained from all subjects involved in the study. Conflict of interest: The authors declare no competing interests.

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