Hepatocellular carcinoma: Gene expression profiling and regulation of xenobiotic-metabolizing cytochromes P450
Jazyk angličtina Země Velká Británie, Anglie Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
32173367
DOI
10.1016/j.bcp.2020.113912
PII: S0006-2952(20)30140-4
Knihovny.cz E-zdroje
- Klíčová slova
- CYP, Cytochrome P450, Drug metabolism, Gene expression, Hepatocellular carcinoma, Non-coding RNA,
- MeSH
- dospělí MeSH
- hepatocelulární karcinom enzymologie patologie MeSH
- hepatocyty metabolismus MeSH
- játra metabolismus MeSH
- kohortové studie MeSH
- lidé středního věku MeSH
- lidé MeSH
- metabolická inaktivace genetika MeSH
- nádory jater enzymologie patologie MeSH
- receptory cytoplazmatické a nukleární genetika metabolismus MeSH
- regulace genové exprese enzymů * MeSH
- senioři MeSH
- stanovení celkové genové exprese MeSH
- stupeň nádoru MeSH
- systém (enzymů) cytochromů P-450 genetika MeSH
- transkriptom * MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- receptory cytoplazmatické a nukleární MeSH
- systém (enzymů) cytochromů P-450 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
Citace poskytuje Crossref.org
Role of miR-653 and miR-29c in downregulation of CYP1A2 expression in hepatocellular carcinoma
