| Abstract [eng] |
Gene Expression Analysis of Metallothionein and Histone Modifying Genes in Prostate Tumors Metallothioneins could protect the cell from UV rays and have ability to inhibit apoptosis. Many studies have shown that expression of metallothionein coding genes varies in many of human tumors. Histone modifying genes encode enzymes which are involved in protein modification reactions and regulate the expression and functions of other genes. A lot of research is performed with treatment and diagnosis of prostate cancer, but this oncological disease remains most diagnosed disease among men of all ages. Achievements of epigenetics are already being used to treat many diseases, so the value of epigenetic markers in diagnosing prostate cancer and predicting disease progression is unquestionable. The aim of this study was to evaluate the expression of metallothionein and histone modifying genes in prostate tumors and non-cancerous prostate tissues and to link them with the clinical-pathological characteristics of patients. Research of gene expression was performed using a quantitative reverse transcriptase polymerase chain reaction. The expression of MT1E, MT1G, MT1M genes was higher in non-cancerous prostate tissues than in tumors (p = 0.1216, p = 0.0055 and p = 0.0040, respectively) or in benign hyperplasia tissues (p = 0.0022, p = 0.0010 and p = 0.0428) and in non-progressive prostate tumors compared to rapidly progressing (p = 0.0292, p = 0.0005, and p = 0.0004). Expression of all these genes was higher in tumors of the previous stage (p = 0.0007, p < 0.0001 and p < 0.0001) and lower ISUP category (p = 0.0283, p = 0.0028 and p < 0.0001). Higher expression of MT1E and MT1G genes was observed in tumors lacking the TMPRSS2-ERG transcript (p = 0.0481 and p = 0.0012). Also, expression of MT1E and MT1M genes was negatively correlated with PSA levels in patients' blood (p = 0.0430, p = 0.0141). KDM5D expression was higher in non-cancerous prostate tissues (p = 0.0165). KDM3A gene expression was higher in prostate tumors compared to hyperplasia tissues, and KMT5A gene expression was higher in hyperplasia tissues (p = 0.0024, p < 0.0001). Higher expression of KDM5D, KMT5A and PHF8 genes was found in the tumors of the previous stage (p = 0.0391, p = 0.0446 and p = 0.0219), and in the 54 case of the PHF8 gene - in tumors of the lower ISUP category (p = 0.0286). Higher expression of KDM5D gene is found in tumors bearing the TMPRSS2-ERG transcript (p = 0.0172) and KDM3A gene expression is positively correlated with patient age (p = 0.0331). Higher expression of PHF8 gene was found in non-progressive tumors compared to rapidly progressing tumors (p = 0.0414), and higher KMT5A gene expression is characterized by non-progressive tumors compared to slow-progressing ones (p = 0.0009). The results suggest that altered expression of metallothionein and histone-modifying genes can be used as a diagnostic marker for prostate cancer, but the potential prognostic value is still in doubt. |
