SIGNIFICANCE OF OSTEOPONTIN FOR PREDICTING AGGRESSIVENESS OF PROSTATE CANCER.

BACKGROUND: Effective prediction of the course of prostate cancer (PCa) and the stratification of treatment tactics largely depend on the use of prognostic markers that reflect the molecular and biological features of tumors. In view of the important role of matricellular proteins in the modulation of the growing tumor and metastasis of the hormone-dependent neoplasms, the aim of the work was to study the expression of osteopontin (OPN) at the protein and mRNA levels in the PCa tissue in order to assess the significance of this protein for predicting the aggressiveness of PCa. MATERIALS AND METHODS: The work is based on the analysis of the results of the examination and treatment of 83 patients with PCa of stages II-IV. The study of OPN expression at the level of mRNA and protein in the PCa tissue was carried out using methods of the real time polymerase chain reaction and immunohistochemistry, respectively. RESULTS: The OPN expression in the PCa tissue was 1.6 times (p < 0.05) higher in patients with regional lymph node metastases compared to patients without metastases. In patients with a Gleason score of < 7, the OPN expression in the tumor tissue was 1.4 times lower (p < 0.05) than in patients with poorly differentiated PCa. In patients with a high risk of tumor progression, the OPN expression level was 1.4 and 2.1 times higher (p < 0.05) compared to patients with a moderate and low risk of PCa progression. The patients with a high OPN expression level in the PCa tissue had significantly decreased 2-year recurrence-free survival rate (by 25%). CONCLUSIONS: The obtained results indicate the expediency of using OPN expression indicators in the tumor tissue to predict the PCa aggressiveness and assess the risk of its recurrence.

EXPRESSION OF MARKERS OF BONE TISSUE REMODELING IN BREAST CANCER AND PROSTATE CANCER CELLS IN VITRO.

The aim of the study was to compare the expression of markers of bone remodeling in vitro in breast cancer (BCa) cells and prostate cancer (PCa) cells varying in their malignancy phenotype. MATERIALS AND METHODS: The study was performed on human BCa cells (MCF-7 and MDA-MB-231 lines) and PCa cells (LNCaP and DU-145 lines). Expression levels of bone tissue remodeling proteins (osteopontin (OPN), osteonectin (ON) and bone morphogenetic protein 7 (BMP-7) were determined immunocytochemically. The mRNA levels of bone tissue remodeling proteins OPN (SPP1), ON (SPARC), BMP-7 (BMP7)) and miRNA-10b, -27a, -29b, -145, -146a were assessed by quantitative reverse transcription polymerase chain reaction. To search for miRNAs involved in the regulation of target genes, miRNet v. 2.0 resource was used. RESULTS: We have shown that highly malignant MDA-MB-231 cells are characterized by significantly higher expression of OPN and ON on the background of decreased SPARC and BMP7 mRNA expression. In highly malignant DU-145 cells, ON and SPP1, SPARC, and BMP7 mRNA expression was significantly higher compared with low malignant LNCaP cells. MDA-MB-231 line was characterized by significantly higher expression of miRNA-10b, -27a, -29b, -145 and -146a. In DU-145 cells, significantly lower levels of expression of miRNAs-27a and -145 against the background of increasing levels of miRNAs-29b and -146a were recorded. CONCLUSION: High malignancy phenotype of the BCa and PCa cells is characterized by high levels of expression of bone remodeling proteins, which may be caused by impaired regulation of their expression at the epigenetic level.

EVALUATION OF DIAGNOSTIC ALGORITHM BASED ON COLLAGEN ORGANIZATION PARAMETERS FOR BREAST TUMORS.

The changes in the quantitative parameters and spatial structure of collagen are considered a key diagnostic and prognostic factor associated with the development of many malignant neoplasms, including breast cancer (BCa). The aim of the work was to develop and test an algorithm for the assessment of collagen organization parameters as informative attributes associated with BCa for developing technology of machine learning and building an intelligent system of cancer diagnostics. MATERIALS AND METHODS: Tumor tissue samples of 5 patients with breast fibroadenomas and 20 patients with stage I-II BCa were studied. Collagen was identified histochemically by Mallory method. Photomicrographs of the studied preparations were obtained using a digital microscopy complex AxioScope A1. Morphometric studies were performed using the software CurveAlign v. 4.0. beta and ImageJ. RESULTS: The algorithm for determining the quantitative characteristics and spatial organization of the collagen matrix in tumor tissue samples has been developed and tested. We showed that collagen fibers in the BCa tissue are characterized by significantly lower values of length (p < 0.001) and width (p < 0.001) as well as higher values of straightness (p < 0.001) and angle (p < 0.05) compared to these in the fibroadenoma tissue. No significant difference was found in the density of collagen fibers in the tissue of benign and malignant neoplasms of the mammary gland. CONCLUSION: The algorithm allows assessing a wide range of parameters of collagen fibers in tumor tissue, including their spatial orientation and mutual arrangement, parametric characteristics and density of the three-dimensional fibrillar network.