Work number - M 37 FILED
Presented RE. Kavetsky National Academy of Sciences of Ukraine
Authors:
ZADVORNYI Taras - candidate of biological sciences, researcher of the laboratory of drug resistance mechanisms of the Institute of Experimental Pathology, Oncology and Radiobiology named after RE. Kavetsky National Academy of Sciences of Ukraine;
TYMOSHENKO Andrii is a graduate student at the Tumor Process Monitoring and Therapy Design Department of the Institute of Experimental Pathology, Oncology and Radiobiology named after RE. Kavetsky National Academy of Sciences of Ukraine.
The work is devoted to the study of molecular, genetic, and epigenetic features of the tumor microenvironment in order to identify panels of biomarkers for predicting the course of prostate cancer (PCа) with a high risk of progression. The research is complex and conducted using in vitro, in silico, and ex vivo systems with the help of clinical, morphological, morphometric, histochemical, immunohistochemical, molecular biological, bioinformatics, and statistical methods.
Experimental studies in the in vitro system have proven that the degree of malignancy of human PCa cells is associated with the level of expression of such immunomodulatory proteins as lactoferrin (LF) and osteonectin(ON), as well as tumor stem cell markers. As a result of a retrospective analysis, it was established that recurrences of PCa are most often diagnosed in the form of distant bone metastases, which are determined in 50.0% of cases, while the presence of metabolic syndrome increases the risk of progression of this form of cancer by 25%. On the clinical material in the ex vivo system, it was found that a characteristic feature of PCa with a high risk of progression is a dysregulation of the expression of immunomodulatory proteins (LF, OPN and ON), which leads to an increase in the infiltration levels of mast cells and tumor-associated fibroblasts and is accompanied by an increase in the degree of stemness by increasing the level of NANOG mRNA. For the first time, the expression pattern of microRNAs that participate in the regulation of microenvironment genes and play a key role in the manifestation of PCa was identified. Based on the method of multiple linear regression, the expediency of using the expression indicators of tumor-associated miR-7-5p, miR-19a-3p, and miR-23b-3p and circulating miR-205 and miR-214 was proven as predictors of the PCa progression risk. As a result of a complex in vitro and ex vivo study, a panel of biomarkers for predicting the aggressiveness of the course of PCa was identified. It has been proven that the use of created panels of biomarkers for predicting the course of PCa with a high risk of progression allows to increase the immediate results of treatment according to the WHO scale by 30 and 40% and leads to an improvement in the life of patients by 12%.
Number of publications: 4 scientific papers, including 2 chapters in collective monographs (including 1 foreign one), 14 articles in Ukrainian and foreign journals included in the category "A" and 8 articles in scientific publications included in the category "B". The total number of references to the authors' publications/h-index of the work, according to the databases, is, respectively: Web of Science – 20/3, Scopus–42/4, Google Scholar –57/4.
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