Cytochrome P450-2D6: A novel biomarker in liver cancer health disparity.

Liver cancer morbidity and mortality rates differ among ethnic groups. In the United States, the burden of liver cancer in Asian Americans (AS) is higher compared to Caucasian Americans (CA). Research on liver cancer health disparities has mainly focused on environmental and socioeconomic factors ye...

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Autores principales:	Zahraa I Khamis, Xiaodong Pang, Zihan Cui, Qing-Xiang Amy Sang, Jinfeng Zhang
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/6b2526295cf04365bf5abdce02df5d81
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id	oai:doaj.org-article:6b2526295cf04365bf5abdce02df5d81
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spelling	oai:doaj.org-article:6b2526295cf04365bf5abdce02df5d812021-12-02T20:13:52ZCytochrome P450-2D6: A novel biomarker in liver cancer health disparity.1932-620310.1371/journal.pone.0257072https://doaj.org/article/6b2526295cf04365bf5abdce02df5d812021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0257072https://doaj.org/toc/1932-6203Liver cancer morbidity and mortality rates differ among ethnic groups. In the United States, the burden of liver cancer in Asian Americans (AS) is higher compared to Caucasian Americans (CA). Research on liver cancer health disparities has mainly focused on environmental and socioeconomic factors yet has ignored the genotypic differences among various racial/ethnic groups. This lack of molecular level understanding has hindered the development of personalized medical approaches for liver cancer treatment. To understand the genetic heterogeneity of liver cancer between AS and CA, we performed a systematic analysis of RNA-seq data of 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 the differentially expressed genes. Our analysis identified cytochrome P450-2D6 enzyme (CYP2D6) as the gene with the greatest differential expression with higher levels in AS compared to CA. To scrutinize 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. Herein, we report that CYP2D6 may serve as a putative biomarker in liver cancer health disparities. Its negative association with IL6 proclaims an intricate relationship between CYP2D6 and inflammation in the ethnic differences seen in AS and CA liver cancer patients. The goal of the present study was to understand how genetic factors may contribute to the interethnic variability of liver cancer prevalence and outcomes in AS and CA patients. Identifying ethnic-specific genes may help ameliorate detection, diagnosis, surveillance, and treatments of liver cancer, as well as reduce disease-related incidence and mortality rates in the vulnerable population.Zahraa I KhamisXiaodong PangZihan CuiQing-Xiang Amy SangJinfeng ZhangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 10, p e0257072 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Zahraa I Khamis Xiaodong Pang Zihan Cui Qing-Xiang Amy Sang Jinfeng Zhang Cytochrome P450-2D6: A novel biomarker in liver cancer health disparity.
description	Liver cancer morbidity and mortality rates differ among ethnic groups. In the United States, the burden of liver cancer in Asian Americans (AS) is higher compared to Caucasian Americans (CA). Research on liver cancer health disparities has mainly focused on environmental and socioeconomic factors yet has ignored the genotypic differences among various racial/ethnic groups. This lack of molecular level understanding has hindered the development of personalized medical approaches for liver cancer treatment. To understand the genetic heterogeneity of liver cancer between AS and CA, we performed a systematic analysis of RNA-seq data of 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 the differentially expressed genes. Our analysis identified cytochrome P450-2D6 enzyme (CYP2D6) as the gene with the greatest differential expression with higher levels in AS compared to CA. To scrutinize 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. Herein, we report that CYP2D6 may serve as a putative biomarker in liver cancer health disparities. Its negative association with IL6 proclaims an intricate relationship between CYP2D6 and inflammation in the ethnic differences seen in AS and CA liver cancer patients. The goal of the present study was to understand how genetic factors may contribute to the interethnic variability of liver cancer prevalence and outcomes in AS and CA patients. Identifying ethnic-specific genes may help ameliorate detection, diagnosis, surveillance, and treatments of liver cancer, as well as reduce disease-related incidence and mortality rates in the vulnerable population.
format	article
author	Zahraa I Khamis Xiaodong Pang Zihan Cui Qing-Xiang Amy Sang Jinfeng Zhang
author_facet	Zahraa I Khamis Xiaodong Pang Zihan Cui Qing-Xiang Amy Sang Jinfeng Zhang
author_sort	Zahraa I Khamis
title	Cytochrome P450-2D6: A novel biomarker in liver cancer health disparity.
title_short	Cytochrome P450-2D6: A novel biomarker in liver cancer health disparity.
title_full	Cytochrome P450-2D6: A novel biomarker in liver cancer health disparity.
title_fullStr	Cytochrome P450-2D6: A novel biomarker in liver cancer health disparity.
title_full_unstemmed	Cytochrome P450-2D6: A novel biomarker in liver cancer health disparity.
title_sort	cytochrome p450-2d6: a novel biomarker in liver cancer health disparity.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/6b2526295cf04365bf5abdce02df5d81
work_keys_str_mv	AT zahraaikhamis cytochromep4502d6anovelbiomarkerinlivercancerhealthdisparity AT xiaodongpang cytochromep4502d6anovelbiomarkerinlivercancerhealthdisparity AT zihancui cytochromep4502d6anovelbiomarkerinlivercancerhealthdisparity AT qingxiangamysang cytochromep4502d6anovelbiomarkerinlivercancerhealthdisparity AT jinfengzhang cytochromep4502d6anovelbiomarkerinlivercancerhealthdisparity
_version_	1718374709433729024

Cytochrome P450-2D6: A novel biomarker in liver cancer health disparity.

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