Cytochrome P450 genes expression in human prostate cancer

Abstract

CYP-dependent metabolites play a critical role in regulating the cell cycle, as well as the proliferative, invasive, and migratory activity of cancer cells. We conducted a study to analyze the relative gene expression of various CYPs (CYP7B1, CYP27A1, CYP39A1, CYP51, CYP1B1, CYP3A5, CYP4F8, CYP5A1, CYP4F2, CYP2J2, CYP2E1, CYP2R1, CYP27B1, CYP24A1) in 41 pairs of prostate samples (tumor and conventional normal tissues) using qPCR. Our analysis determined significant individual variability in the expression levels of all studied CYPs, both in the tumor and in conventionally normal groups. However, when we performed a paired test between the tumor and normal groups, we found no significant difference in the expression of the studied genes. We did observe a tendency to increase the level of CYP1B1 expression in the tumor group. We also did not find any significant difference between the levels of the studied CYPs in the tumor and conventional normal groups at different stages of prostate cancer and pathomorphological indicators. Correlation analysis revealed the presence of a positive relationship between the expressions of some cholesterol-metabolizing CYP genes, as well as between genes responsible for vitamin D biosynthesis and cholesterol biosynthesis. We observed significant correlative relationships between the expression of CYPs and some prostate cancer-related genes (CDH2, MMP9, SCHLAP1, GCR, CYP17A1, ACTA2, CXCL14, FAP, CCL17, MSMB, IRF1, VDR). Therefore, the expression of CYPs is not directly associated with prostate cancer but is largely determined by genetic, epigenetic factors, as well as endogenous substrates and xenobiotics. The significant correlative relationship between CYPs and genes associated with cancer may indicate common regulatory pathways that may have a synergistic effect on the tumor, ensuring the survival of cancer cells.

Keywords

• Cytochrome P450
• CYPs
• Prostate cancer