Zadvorny T. Molecular biological features associated with the malignancy degree of prostate cancer

The dissertation is devoted to the actual problem of oncology – identification of molecular-biological and epigenetic biomarkers of human prostate cancer (PC), associated with the aggressiveness of the tumor process. In the in vitro experimental system, phenotypic and molecular-biological features of human PC cell lines of various degrees of malignancy were identified. It was determined that the LNCaP and DU-145 cells lines differ significantly in proliferative activity, adhesive and invasive properties. It was found that the malignancy degree of human PC cell lines is associated with the level of expression of markers CSC and LF, as well as significantly higher expression of oncogenic miR-21, -199a, -205, -214 and a decrease in the level of oncosuppressive miR-320. Ex vivo clinical evidence demonstrated an association between LF expression and CSC markers and the degree of PC malignancy. It was found that low LF expression correlates with an increase in the PC stage (r = -0.55; p <0.05), an increase in the size of tumors (ρ = -0.48; p <0.05), the presence of metastases in RLV(r = -0.52; p <0.05) and an increase in the level of PSA in patients serum (ρ = -0.39; p <0.05). It was found that the presence of cells with the CSC phenotype (CD44+/highCD24-/low) and high levels of NANOG miR expression in tumor tissue are characteristics of patients with an unfavorable course of PC, which has a high malignancy degree in clinical and pathological indicators. The overall 2-year recurrence-free survival of PC patients was significantly lower in the presence of CSC markers (CD44+/highCD24-/low, NANOG mRNA ≥ 4 u.a.) and the absence of LF expression in tumor cells (p<0.05). The relationship between the expression of circulating and tumor miR-205 and miR-214 with the PC malignancy degree and such clinical and pathological characteristics of patients as tumor process stage (p<0.05), metastases in regional lymph nodes (p<0.05), the Gleason score (p<0.05) and preoperative PSA level in blood serum (p<0.05) was shown. The obtained results indicate the potential possibility of using LF levels, CSC markers, miR-205 and miR-214 to predict the aggressiveness of the PC course and to estimate the risk of disease recurrence.