Cytochrome P450 2A6 is associated with macrophage polarization and is a potential biomarker for hepatocellular carcinoma,FEBS Open Bio

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Cytochrome P450 2A6 is associated with macrophage polarization and is a potential biomarker for hepatocellular carcinoma
FEBS Open Bio ( IF 2.8 ) Pub Date : 2021-01-17 , DOI: 10.1002/2211-5463.13089
Tao Jiang ₁ , Ai-Song Zhu ₁ , Chu-Qi Yang ₁ , Chu-Yun Xu ₁ , Dan-Qian Yang ₁ , Zhao-Huan Lou ₂ , Guang-Ji Zhang ₁

Affiliation

Cytochrome P450 2A6 (CYP2A6) is an important metabolic enzyme and is involved in the progression of hepatocellular carcinoma (HCC). However, its specific function and the mechanism of modulation remain to be elucidated. In this study, we found that CYP2A6 is dramatically downregulated in HCC. CYP2A6 expression is closely associated with pathological grading, histologic grade, hepatitis, vascular metastasis, liver inflammation, and worse prognosis. Reduced expression of CYP2A6 contributes to alternative activation of macrophage polarization and impairs macrophage maturation and phagocytosis. Mechanistically, CYP2A6 participates in arachidonic acid metabolism, initiates 20‐hydroxyeicosatetraenoic acid (HETE) generation, and inhibits epoxyeicosatrienoic acid (EET) generation. Disruption of the equilibrium between 20‐HETE and EETs can induce macrophage polarization, thereby modulating antitumor immunity.

中文翻译：

细胞色素 P450 2A6 与巨噬细胞极化相关，是肝细胞癌的潜在生物标志物

细胞色素 P450 2A6 (CYP2A6) 是一种重要的代谢酶，参与肝细胞癌 (HCC) 的进展。然而，其具体功能和调制机制仍有待阐明。在这项研究中，我们发现 CYP2A6 在 HCC 中显着下调。CYP2A6的表达与病理分级、组织学分级、肝炎、血管转移、肝脏炎症及不良预后密切相关。CYP2A6 的表达降低有助于巨噬细胞极化的替代激活并损害巨噬细胞成熟和吞噬作用。从机制上讲，CYP2A6 参与花生四烯酸代谢，启动 20-羟基二十碳四烯酸 (HETE) 的生成，并抑制环氧二十碳三烯酸 (EET) 的生成。

更新日期：2021-03-04

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