| Abstract [eng] |
Prostate carcinoma is the second most common cancer and the fifth leading cause of death from cancer among men. Implementation of prostate-specific antigen (PSA) testing into clinical practice led to a marked increase in the numbers of newly diagnosed early stage prostate cancer. However, even localized prostate adenocarcinoma is a highly heterogeneous disease with variable clinical outcomes ranging from indolent, low-risk disease to tumors with aggressive behavior having a tendency to progress. The risk evaluation based on D’Amico’s classification system (clinical stage, PSA level, and histological features of the tumor on the biopsy) is also not adequately informative, with nearly one half of cases being upgraded/upstaged at final pathology. Molecular markers may provide more accurate measures of tumor aggressiveness and assist in the discrimination between indolent forms of prostate adenocarcinomas and clinically aggressive tumors. This study aimed at identification of new prognostic biomarkers of prostate adenocarcinoma in order to develop molecular diagnostic tools for prostate tumors sub-typing into aggressive and slowly growing, indolent prostate cancer. In this work was used an innovative assay approach that includes application of modern molecular tools: microarray and quantitative PCR. For the first time, detailed analysis of the expression of 50 different ABC transporters in prostate cancer biosamples has been performed. The influence of metallothionein genes on the development of prostate cancer has been poorly studied, and there is no data on the expression of the MT1E gene in prostate adenocarcinoma tissue. For the first time, we showed an association between the MT1E gene expression and prostate cancer progression. Moreover, we assessed the mechanism of gene down-regulation by promoter DNA methylation. New potential molecular biomarkers have been studied that can assist in prediction of disease progression and reliable discrimination of tumor tissues from non-tumor ones. |
