Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450

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Publikace nespadá pod Lékařskou fakultu, ale pod Středoevropský technologický institut. Oficiální stránka publikace je na webu muni.cz.

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NEKVINDOVA J. MRKVICOVA A. ZUBANOVA V. VACULOVA A.H. ANZENBACHER P. SOUCEK P. RADOVÁ Lenka SLABÝ Ondřej KISS Igor VONDRACEK J. SPICAKOVA A. BOHOVICOVÁ Lucia FABIAN P. KALA Z. PALICKA V.

Rok publikování 2020
Druh Článek v odborném periodiku
Časopis / Zdroj Biochemical Pharmacology
Fakulta / Pracoviště MU

Středoevropský technologický institut

Citace
www https://www.sciencedirect.com/science/article/pii/S0006295220301404?via%3Dihub
Doi http://dx.doi.org/10.1016/j.bcp.2020.113912
Klíčová slova Hepatocellular carcinoma; Cytochrome P450; CYP; Drug metabolism; Gene expression; Non-coding RNA
Popis Hepatocellular carcinoma (HCC) remains a highly prevalent and deadly disease, being among the top causes of cancer-related deaths worldwide. Despite the fact that the liver is the major site of biotransformation, studies on drug metabolizing enzymes in HCC are scarce. It is known that malignant transformation of hepatocytes leads to a significant alteration of their metabolic functions and overall deregulation of gene expression. Advanced stages of the disease are thus frequently associated with liver failure, and severe alteration of drug metabolism. However, the impact of dysregulation of metabolic enzymes on therapeutic efficacy and toxicity in HCC patients is largely unknown. Here we demonstrate a significant down-regulation in European Caucasian patients of cytochromes P450 (CYPs), the major xenobiotic-metabolizing enzymes, in HCC tumour samples as compared to their surrounding non-cancerous (reference) tissue. Moreover, we report for the first time the association of the unique CYP profiles with specific transcriptome changes, and interesting correlations with expression levels of nuclear receptors and with the histological grade of the tumours. Integrated analysis has suggested certain co-expression profiles of CYPs with lncRNAs that need to be further characterized. Patients with large tumours with down-regulated CYPs could be more vulnerable to drug toxicity; on the other hand, such tumours would eliminate drugs more slowly and should be more sensitive to pharmacotherapy (except in the case of pro-drugs where activation is necessary).

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