Downregulation of CYP2A6 and CYP2C8 in Tumor Tissues Is Linked to Worse Overall Survival and Recurrence-Free Survival from Hepatocellular Carcinoma

Ren, Xiaojing; Ji, Yuanyuan; Jiang, Xuhua; Qi, Xun

doi:10.1155/2018/5859415

Cited by 31 publications

(29 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Thus, Trujillo-Paolillo et al [51] have demonstrated that Osteosarcoma biopsy specimens has lower CYP3A4 levels than normal bone specimens. Similar findings have been found for CYP3A4 in Hepatocellular Carcinoma tissues as compared to paired adjacent noncancerous liver tissues [52, 53].…”

Section: Discussionsupporting

confidence: 85%

Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells

et al. 2019

View full text Add to dashboard Cite

Thyroid hormones (THs) – 3,3′,5-triiodo-L-thyronine (T3) and L-thyroxine (T4) – are important regulators of the metabolism and physiology of most normal tissues. Cytochrome P450 family 3A members are drug metabolizing enzymes involved in the activation and detoxification of several drugs. CYP3A4 is the major enzyme involved in the metabolism of chemotherapeutic drugs. In this work, we demonstrate that THs induce a significant increase in CYP3A4 mRNA levels, protein expression and metabolic activity through the membrane receptor integrin αvβ3 and the activation of signalling pathways through Stat1 and NF-κB. We reasoned that TH-induced CYP3A4 modulation may act as an important regulator in the metabolism of doxorubicin (Doxo). Experiments in vitro demonstrated that in CYP3A4-knocked down cells, no TH-mediated chemosensitivity to Doxo was observed. We also found that THs modulate these functions by activating the membrane receptor integrin αvβ3. In addition, we showed that the thyroid status can modulate CYP450 mRNA levels in tumor and liver tissues, and the tumor volume in response to chemotherapy in vivo . In fact, Doxo treatment in hypothyroid mice was associated with lower tumors, displaying lower levels of CYP enzymes, than euthyroid mice. However, higher mRNA levels of CYP enzymes were found in livers from Doxo treated hypothyroid mice respect to control. These results present a new mechanism by which TH could modulate chemotherapy response. These findings highlight the importance of evaluating thyroid status in patients during application of T-cell lymphoma therapeutic regimens.

show abstract

Section: Discussionsupporting

confidence: 85%

Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The expression levels of CYP2A6 and CYP2A7 are lower in patients with hepatitis B virus and HCV than those in healthy people [41]. Moreover, patients with HCC with downregulated CYP2A6 exhibit the worse OS [42]. In the present study, the expression levels of CYP2A6 and CYP2A7 were low and negatively correlated with tumor stages and grades.…”

Section: Discussionsupporting

confidence: 45%

Comprehensive Analysis of the Expression and Prognosis of 12 Cytochrome P450s in Human Hepatocellular Carcinoma from the Perspective of Network Pharmacology

Jiang

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: Cytochrome P450s (CYPs) are pivotal drug metabolic enzymes and play a crucial part in the development and prognosis of hepatocellular carcinoma (HCC). Among various CYPs, 12 (CYP1A2, 27A1, 2A6, 2A7, 2B6, 2C8, 2C9, 2E1, 2J2, 3A4, 3A5, and 4A11) are recognized as key therapeutic targets for HCC from the perspective of network pharmacology. However, the gene expression and prognosis of these 12 CYPs in HCC remain obscure.Methods: In the current study, the mRNA expression of these 12 CYPs and survival of patients with HCC were investigated by mining data from ONCOMINE, Kaplan–Meier plotter, UALCAN, Human Protein Atlas, cBioPortal, STRING, and DAVID databases. Network pharmacology analysis of sorafenib for HCC treatment was conducted using data from Therapeutic Target Database, Drugbank, Swiss Target Prediction, STITCH, OncoDB.HCC, Liverome, STRING, and DAVID databases.Results: Results showed that the mRNA expression levels of the 12 CYPs were markedly reduced in HCC and negatively correlated with tumor stages and grades (except for CYP3A5). The high expression level of nine CYPs, namely, CYP27A1, 2A6, 2A7, 2C8, 2C9, 2E1, 3A4, 3A5, and 4A11 was significantly correlated with favorable prognosis in patients with HCC, indicating that they may serve as candidate prognostic biomarkers for HCC. Additionally, overexpression of CYP27A1, CYP2A7, CYP2B6, CYP2C9, and CYP3A5 was markedly correlated with favorable overall survival in HCC patients who received sorafenib therapy. Network pharmacology analysis of the administration of sorafenib for HCC treatment suggested that this drug may exert its antihepatocarcinoma effects by regulating the FoxO and ErbB signaling pathways.Conclusion: Characterization of the expression and prognosis of 12 CYPs in HCC, as well as network pharmacology analysis of HCC treatment via sorafenib, may provide novel insights into the discovery of potential prognostic markers of and therapeutic targets in HCC.

show abstract

“…Studies have pointed out that CYP450 family genes are signi cantly associated with liver disease and liver cancer. For example, the downregulation of CYP2A6 and CYP2C8 is related to the overall survival and recurrence rates of liver cancer [38]. Additionally, the high expression of CYP4A11 is associated with a better prognosis in patients with liver cancer [39], and CYP activity is affected in varying degrees in patients with liver brosis or cirrhosis.…”

Section: Discussionmentioning

confidence: 99%

FCN3 Is a Prognostic Biomarker Correlated with Immune Response in Liver Cancer

Lu¹,

Wu²,

Yiming³

et al. 2020

Preprint

View full text Add to dashboard Cite

AimLiver cancer is a common malignant tumor whose molecular pathogenesis remains unclear. This study attempts to identify key genes related to liver cancer by bioinformatics analysis and analyze their biological functions.MethodsThe gene expression data of the microarray were downloaded from the Gene Expression Omnibus(GEO) database. The differentially expressed genes (DEGs) were then identified by the R software package “limma” and were subjected to gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses using DAVID. The protein-protein interaction (PPI) network was constructed via String, and the results were visualized in Cytoscape. Modules and hub genes were identified using the MCODE plugin, while the expression of hub genes and its effects were analyzed by GEPIA2. Additionally, the co-expression of the hub gene was explored in String, while the GO results were visualized using the R software. Finally, the targets of the hub gene were predicted through an online website. ResultsIn total, 43 differentially expressed genes were obtained. The GO analysis was mainly concentrated in the redox process and nuclear mitosis, while the KEGG pathway analysis was mainly enriched in retinol metabolism and the cell cycle. Moreover, four hub genes were identified in the PPI network, however, the Kaplan-Meier risk curve showed that only ECT2 and FCN3 affected the survival of liver cancer. ECT2 was found to be high expressed in liver cancer, carrying out signal transduction and targeting hsa-miR-27a-3p. FCN3 was observed to be lowly expressed in liver cancer and related to the immune response, targeting hsa-miR132-5p.ConclusionThe obtained findings suggest that two genes are significantly related to the prognosis of liver cancer, and the analysis of their biological function provided novel insight into the pathogenesis of liver cancer. Furthermore, FCN3 may serve as a promising biomarker for patients with liver cancer.

show abstract

Downregulation of CYP2A6 and CYP2C8 in Tumor Tissues Is Linked to Worse Overall Survival and Recurrence-Free Survival from Hepatocellular Carcinoma

Cited by 31 publications

References 33 publications

Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells

Thyroid hormones induce doxorubicin chemosensitivity through enzymes involved in chemotherapy metabolism in lymphoma T cells

Comprehensive Analysis of the Expression and Prognosis of 12 Cytochrome P450s in Human Hepatocellular Carcinoma from the Perspective of Network Pharmacology

FCN3 Is a Prognostic Biomarker Correlated with Immune Response in Liver Cancer

Contact Info

Product

Resources

About