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

J 2020

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

NEKVINDOVA, J., A. MRKVICOVA, V. ZUBANOVA, A.H. VACULOVA, P. ANZENBACHER et. al.

Basic information

Original name

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

Authors

NEKVINDOVA, J., A. MRKVICOVA, V. ZUBANOVA, A.H. VACULOVA, P. ANZENBACHER, P. SOUCEK, Lenka RADOVÁ (203 Czech Republic, belonging to the institution), Ondřej SLABÝ (203 Czech Republic, belonging to the institution), Igor KISS (203 Czech Republic, belonging to the institution), J. VONDRACEK, A. SPICAKOVA, Lucia BOHOVICOVÁ (203 Czech Republic, belonging to the institution), P. FABIAN, Z. KALA and V. PALICKA

Edition

Biochemical Pharmacology, OXFORD, PERGAMON-ELSEVIER SCIENCE LTD, 2020, 0006-2952

Other information

Language

English

Type of outcome

Článek v odborném periodiku

Field of Study

30104 Pharmacology and pharmacy

Country of publisher

United Kingdom of Great Britain and Northern Ireland

Confidentiality degree

není předmětem státního či obchodního tajemství

References:

URL

Impact factor

Impact factor: 5.858

RIV identification code

RIV/00216224:14740/20:00118001

Organization unit

Central European Institute of Technology

DOI

http://dx.doi.org/10.1016/j.bcp.2020.113912

UT WoS

000541248000005

Keywords in English

Hepatocellular carcinoma; Cytochrome P450; CYP; Drug metabolism; Gene expression; Non-coding RNA

Abstract

V originále

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).

Citovat

NEKVINDOVA, J., A. MRKVICOVA, V. ZUBANOVA, A.H. VACULOVA, P. ANZENBACHER, P. SOUCEK, Lenka RADOVÁ, Ondřej SLABÝ, Igor KISS, J. VONDRACEK, A. SPICAKOVA, Lucia BOHOVICOVÁ, P. FABIAN, Z. KALA and V. PALICKA. Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450. Biochemical Pharmacology. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2020, vol. 177, JUL, p. 113912-113922. ISSN 0006-2952. Available from: https://dx.doi.org/10.1016/j.bcp.2020.113912.

@article{1733371,
   author = {Nekvindova, J. and Mrkvicova, A. and Zubanova, V. and Vaculova, A.H. and Anzenbacher, P. and Soucek, P. and Radová, Lenka and Slabý, Ondřej and Kiss, Igor and Vondracek, J. and Spicakova, A. and Bohovicová, Lucia and Fabian, P. and Kala, Z. and Palicka, V.},
   article_location = {OXFORD},
   article_number = {JUL},
   doi = {http://dx.doi.org/10.1016/j.bcp.2020.113912},
   keywords = {Hepatocellular carcinoma; Cytochrome P450; CYP; Drug metabolism; Gene expression; Non-coding RNA},
   language = {eng},
   issn = {0006-2952},
   journal = {Biochemical Pharmacology},
   title = {Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450},
   url = {https://www.sciencedirect.com/science/article/pii/S0006295220301404?via%3Dihub},
   volume = {177},
   year = {2020}
}

TY  - JOUR
ID  - 1733371
AU  - 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.
PY  - 2020
TI  - Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450
JF  - Biochemical Pharmacology
VL  - 177
IS  - JUL
SP  - 113912
EP  - 113912
PB  - PERGAMON-ELSEVIER SCIENCE LTD
SN  - 00062952
KW  - Hepatocellular carcinoma
KW  - Cytochrome P450
KW  - CYP
KW  - Drug metabolism
KW  - Gene expression
KW  - Non-coding RNA
UR  - https://www.sciencedirect.com/science/article/pii/S0006295220301404?via%3Dihub
L2  - https://www.sciencedirect.com/science/article/pii/S0006295220301404?via%3Dihub
N2  - 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).
ER  -

NEKVINDOVA, J., A. MRKVICOVA, V. ZUBANOVA, A.H. VACULOVA, P. ANZENBACHER, P. SOUCEK, Lenka RADOVÁ, Ondřej SLABÝ, Igor KISS, J. VONDRACEK, A. SPICAKOVA, Lucia BOHOVICOVÁ, P. FABIAN, Z. KALA and V. PALICKA. Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450. \textit{Biochemical Pharmacology}. OXFORD: PERGAMON-ELSEVIER SCIENCE LTD, 2020, vol.~177, JUL, p.~113912-113922. ISSN~0006-2952. Available from: https://dx.doi.org/10.1016/j.bcp.2020.113912.

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