Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450
Language English Country Great Britain, England Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
32173367
DOI
10.1016/j.bcp.2020.113912
PII: S0006-2952(20)30140-4
Knihovny.cz E-resources
- Keywords
- CYP, Cytochrome P450, Drug metabolism, Gene expression, Hepatocellular carcinoma, Non-coding RNA,
- MeSH
- Adult MeSH
- Carcinoma, Hepatocellular enzymology pathology MeSH
- Hepatocytes metabolism MeSH
- Liver metabolism MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Inactivation, Metabolic genetics MeSH
- Liver Neoplasms enzymology pathology MeSH
- Receptors, Cytoplasmic and Nuclear genetics metabolism MeSH
- Gene Expression Regulation, Enzymologic * MeSH
- Aged MeSH
- Gene Expression Profiling MeSH
- Neoplasm Grading MeSH
- Cytochrome P-450 Enzyme System genetics MeSH
- Transcriptome * MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Receptors, Cytoplasmic and Nuclear MeSH
- Cytochrome P-450 Enzyme System MeSH
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).
Central European Institute of Technology Masaryk University Brno Czech Republic
Department of Oncological and Experimental Pathology Cancer Institute Brno Czech Republic
Department of Surgery University Hospital Brno Czech Republic
References provided by Crossref.org
Role of miR-653 and miR-29c in downregulation of CYP1A2 expression in hepatocellular carcinoma
