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. 2024 Jan 9:38:101049.
doi: 10.1016/j.ymgmr.2024.101049. eCollection 2024 Mar.

Cytochrome P450 genes expression in human prostate cancer

Oksana Maksymchuk  1 , Ganna Gerashchenko  1 , Inna Rosohatska  1 , Oleksiy Kononenko  2 , Andriy Tymoshenko  2 , Eduard Stakhovsky  2 , Volodymyr Kashuba  1
Affiliations

Cytochrome P450 genes expression in human prostate cancer

Oksana Maksymchuk et al. Mol Genet Metab Rep. .

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: CYPs; Cytochrome P450; Prostate cancer.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Fig. 1
Fig. 1
The relative expression levels of CYP genes involved in the metabolism of polyunsaturated fatty acids in pairs of tissue samples of the human prostate gland. (A) CYP2E1, (B) CYP2J2, (C) CYP4F8, (D) CYP4F2. The horizontal axis represents the number of tissue sample pairs (T/CNT). T – tumor, CNT – conventionally normal tissue samples.
Fig. 2
Fig. 2
The relative expression levels of CYP genes involved in the metabolism of cholesterol, testosterone and xenobiotics in pairs of tissue samples of the human prostate gland. (A) CYP1B1, (B) CYP7B1, (C) CYP5A1, (D) CYP39A1, (E) CYP51, (F) CYP3A5. The horizontal axis represents the number of tissue sample pairs (T/CNT). T – tumor, CNT – conventionally normal tissue samples.
Fig. 3
Fig. 3
The relative expression levels of CYP genes involved in the metabolism of vitamin D in pairs of tissue samples of the human prostate gland. (A) CYP2R1, (B) CYP27B1, (C) CYP24A1, (D) CYP27A1. The horizontal axis represents the number of tissue sample pairs (T/CNT). T – tumor, CNT – conventionally normal tissue samples.
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