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Alisa Villert

Cancer Research Institute of TNMRC, Russian Federation

Title: Ascitis as a unique microenvironment of tumors in ovarian cancer: interaction with prognosis and chemoresistance

Abstract

Ascitic fluid is an attractive biological fluid for searching for molecular biomarkers that characterize the tumor microenvironment in ovarian cancer (OC). In a group of 41 patients with High Grade (HG) OC, firstly, we studied the parameters of the insulin-like growth factors system – IFR-I, IFR-II and insulin-like growth factor receptor type I and metalloproteinase PAPP-A. It was revealed that the level of IGF system proteins depends on the volume of ascitic fluid. The maximum level of IGF-II and PAPP-A was detected in patients with a moderate amount of ascites (from 200 to 1000 ml). With large amounts of ascitic fluid (>1000 ml), high levels of PAPP-A were observed, but the level of both growth factors, especially IGF-II, decreased (p < 0.05). The differences in the studied parameters in ascitic fluid depending on the status of the BRCA1,2 genes concerned primarily the level of IGF-2 (it was lower in mBRCA patients). Regardless of the BRCA1,2 gene status, IGF-2 levels in ascitic fluid below 60.0 ng/mg protein are associated with a significant increase in 5-year overall survival rates. Correlations between the levels of IGFs in the primary tumor tissue, metastatic disseminates and ascitic fluid were traced. Secondly, we studied extracellular vesicles (exosomes) in ascites, assessing their protease activity. Exosomes of ascitic fluid and blood plasma of patients with HG OC compared with patients with borderline ovarian tumors contain significant amounts of 20S proteasomes, which do not have chymotrypsin-like activity. Their level correlates with the level of 20S proteasomes in the primary tumor tissue and with the volume of ascitic fluid. Therefore, the molecular genetic components of ascitic fluid are related to the prognosis of HG ovarian cancer and may be of particular interest for future studies.

Biography

Alisa Villert is a senior researcher at the Department of Gynecology, Research Institute of Oncology, Tomsk National Research Medical Center, Russia. She completed her PHD at Tomsk National Research Medical Center, Russia, in 2022. It was focused on the study of prognostic factors for ovarian cancer. Hereditary and molecular genetic parameters in ovarian cancer are of greatest scientific interest since 2014. She is an operating gynecological oncologist with 20 years of clinical and scientific experience. She has all the skills of open and laparoscopic surgery in gynecological oncology, and is engaged in advanced, functionally sparing and organ-preserving operations for gynecological cancer. She has over 80 publications that have been cited over 250 times and has a publication H-index of 6 (Scopus).