Expression of proliferationand apoptosis-related genes in hpv-infected pregnant women

Background. Cervical intraepithelial neoplasia (CIN) occurs in 1.3 to 2.7 cases per 1000 pregnancies, and the incidence of cervical cancer (CC) is 0.1-12 per 10,000 pregnancies. Changes in the expression of genes of various signaling pathways can serve as a prognostic factor for the transition of CIN to cancer. However, these processes are insufficiently studied, especially in pregnant women, which served as the basis for this study. Objective. Determination of the expression of proliferation- and apoptosis-related genes in pregnant women infected with human papillomaviruses (HPV) and their role in predicting the progression of cervical neoplasia. Methods. An open-label observational non-interventional cohort clinical study was conducted. 82 pregnant women infected with HPV were examined. Control group consisted of 25 pregnant women without HPV. All participants underwent general clinical examination, Kvant-21 test to determine the types of HPV, cytological examination of cervical smears, determination of the mRNA expression of the VEGFA, TGFb, BCL-2, BAG1, BAX genes in the epithelial cells of the cervical canal by the real-time polymerase chain reaction. Results. The expression of proliferation-related genes - VEGFA (in the presence of HPV-16, -39, and -58), TGF-b (HPV-16, -33, -39 and -59), BCL-2 (HPV-16, -52 and -58), BAG-1 (HPV-16, -31, -35, -58, and-87) was significantly higher compared to control. With LSIL (low grade squamous intraepithelial lesion), the expression of the VEGFA gene increased, and with HSIL (high grade squamous intraepithelial lesion), expression of all genes (except BAX) increased. So, the ability of some HPV types to change the expression of proliferation-related genes was revealed, but no changes in the expression of the BAX gene, which controls apoptosis, were observed. Conclusion. The most pronounced ability to change the expression of proliferation-related genes is possessed by HPV-16 and -58. In LSIL, an increase in the expression of only the VEGFA gene was revealed, in HSIL - increase in expression of all genes characterizing the proliferative potential. No changes in the expression of the BAX gene, which stimulates apoptosis, were found in HPV-infected pregnant women. The results of the study indicate the possibility of using these markers in predicting the progression of cervical lesions, but further research is required.

TGFb, BCL-2, BAG1, BAX, pregnancy, human papillomavirus, cervical diseases, proliferation- and apoptosis-related genes, VEGFA, TGFb, BCL-2, BAG1, BAX