D.O. Utkin1, V.I. Loginov2, D.N. Kushlinsky3, N.Yu. Sokolov4, A.I. Koltunova5, N.A. Arzhanukhina6, D.V. Rogozhin7, J.G. Pajanidi8, E.A. Braga9
1,4–8 Blokhin National Medical Research Center of Oncology,
Ministry of Health of the Russian Federation (Moscow, Russia)
1 Moscow City Oncology Hospital №62 (Moscow, Russia)
2,9 Institute of General Pathology and Pathophysiology (Moscow, Russia)
3 Institute for advanced training of healthcare professionals of the Ministry of Health
of the Khabarovsk Territory (Khabarovsk, Russia)
Formulation of the problem. Blockade of the PD-1/PD-L1 immune checkpoint enhances antitumor immunity by suppressing regulatory (suppressor) T cells and restoring effector T cells. There is literature evidence that microRNAs have an important role, which can inhibit genes regulating the checkpoint of immunity PD-1/PD-L1.
The purpose of the work is to analyze the association of the expression level of a group of microRNA genes in tumors and peritoneal metastases of ovarian cancer patients with the content of soluble forms of PD-1 (sPD-1) and PD-L1 (sPD-L1) in blood plasma to identify new markers associated with the progression and prognosis of the disease.
Results. A significant association was established between a decrease in the expression levels of microRNA genes in tumors with a decrease in the degree of differentiation for the MIR127 gene (p=0.07), with the appearance of ascites for the MIR148 gene (p=0.003), with the appearance of metastases in the large omentum for the MIR339 gene (p<0.05), with tumor dissemination along the peritoneum for the gene MIR127 (p<0.05). The best risk-free survival was observed in patients with RS at "high" levels of MIR191 microRNA gene expression (median 8.5 months) and, conversely, at "low" levels of MIR132 microRNA gene expression (median 8.9 months) and MIR137 (median 10.5 months).
Practical significance. The expression levels of some microRNA genes can be used to assess the prevalence of the disease and predict progression free survival.
Utkin D.O., Loginov V.I., Kushlinsky D.N., Sokolov N.Yu., Koltunova A.I., Arzhanukhina N.A., Rogozhin D.V., Pajanidi J.G., Braga E.A. miRNAs in the regulation of the PD-1/PD-L1 immune checkpoint in ovarian cancer. Technologies of Living Systems. 2023.
V. 20. № 3. Р. 55-64. DOI: https://doi.org/10.18127/j20700997-202303-07 (In Russian).
- Zaridze D.G., Kaprin A.D., Stilidi I.S. Dinamika zabolevayemosti zlokachestvennymi novoobrazovaniyami i smertnosti ot nikh v Rossii. Voprosy onkologii. 2018. T. 64. №. 5. S. 578–591. (in Russian).
- Kaprin A.D. i dr. Zlokachestvennyye novoobrazovaniya zhenskikh polovykh organov v Rossii: situatsiya i problemy. Arkhiv akusherstva i ginekologii im. VF Snegireva. 2014. T. 1. № 2. S. 44–47. (in Russian).
- Armstrong D.K. et al. NCCN guidelines® insights: ovarian cancer, version 3.2022: featured updates to the NCCN guidelines. Journal of the National Comprehensive Cancer Network. 2022. V. 20. № 9. P. 972–980.
- Omar H.A. et al. Immunomodulatory MicroRNAs in cancer: targeting immune checkpoints and the tumor microenvironment. The FEBS Journal. 2019. V. 286. № 18. P. 3540–3557.
- Kushlinskiy N.E. i dr. Covremennyye podkhody k immunoterapii raka pochki. Onkourologiya. 2018. T. 14. № 2. S. 54–67. (in Russian).
- Korotayeva A.A. i dr. Sovremennyye dostizheniya v immunoterapii raka pochki. Onkourologiya. 2019. № 4. S. 30–38. (in Russian).
- Wang Q. et al. The roles of microRNAs in regulating the expression of PD-1. PD-l1 immune checkpoint. 2017.
- Fernandez-Cuesta L. et al. Identification of circulating tumor DNA for the early detection of small-cell lung cancer. EBioMedicine. 2016. V. 10. P. 117–123.
- Wozniak M.B. et al. Circulating microRNAs as non-invasive biomarkers for early detection of non-small-cell lung cancer. PloS one. 2015. V. 10. № 5. P. e0125026.
- Kurman R.J., Carcangiu M.L., Herrington C.S. World Health Organisation classification of tumours of the female reproductive organs. International agency for research on cancer. 2014.
- Hattermann K. et al. A methylation-specific and SYBR-green-based quantitative polymerase chain reaction technique for O6-methylguanine DNA methyltransferase promoter methylation analysis. Analytical biochemistry. 2008. V. 377. № 1. P. 62–71.
- Panagopoulou M. et al. Circulating cell-free DNA in breast cancer: size profiling, levels, and methylation patterns lead to prognostic and predictive classifiers. Oncogene. 2019. V. 38. № 18. P. 3387–3401.
- Loginov V.I. et al. Novel miRNA genes deregulated by aberrant methylation in ovarian carcinoma are involved in metastasis. Gene. 2018. V. 662. P. 28–36.
- Braga E.A. et al. Five hypermethylated microRNA genes as potential markers of ovarian cancer. Bulletin of Experimental Biology and Medicine. 2018. V. 164. P. 351–355.