Cytochrome P450-2D6: a new biomarker in the health disparity of liver cancer

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PLoS One. Oct 1, 2021; 16 (10): e0257072. doi: 10.1371 / journal.pone.0257072. Electronic collection 2021.

ABSTRACT

Morbidity and mortality rates from liver cancer differ among ethnic groups. In the United States, the burden of liver cancer among Asian Americans (AS) is higher than among Caucasian Americans (CA). Research on liver cancer health disparities has mainly focused on environmental and socio-economic factors, but ignored genotypic differences between various racial / ethnic groups. This lack of understanding at the molecular level has hampered the development of personalized medical approaches to the treatment of liver cancer. To understand the genetic heterogeneity of liver cancer between AS and CA, we performed a systematic analysis of RNA-seq data from AS and CA patients from The Cancer Genome Atlas (TCGA). We used four differential gene expression analysis packages; DESeq2, limma, edgeR and Superdelta2, to identify differentially expressed genes. Our analysis identified the cytochrome P450-2D6 enzyme (CYP2D6) as the gene with the greatest differential expression with higher levels in AS versus CA. To examine the underlying mechanism of CYP2D6, Ingenuity Pathway Analysis (IPA) and Cytoscape were conducted and found hepatocyte nuclear factor 4α (HNF4A) and interleukin-6 (IL6) in direct association with CYP2D6 . IL6 is downregulated in AS compared to CA, while HNF4A is not significantly different. Here we report that CYP2D6 may serve as a putative biomarker in liver cancer health disparities. Its negative association with IL6 proclaims a complex relationship between CYP2D6 and inflammation in the ethnic differences seen in patients with AS and CA liver cancer. The objective of the present study was to understand how genetic factors may contribute to interethnic variability in the prevalence and outcome of liver cancer in patients with AS and CA. Identifying specific ethnic genes can help improve detection, diagnosis, surveillance and treatment of liver cancer, as well as reduce disease incidence and mortality rates in the vulnerable population.

PMID: 34597305 | DOI: 10.1371 / journal.pone.0257072


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