Open AccessCytochrome P450 2A6 is associated with macrophage polarization and is a potential biomarker for hepatocellular carcinoma
Author(s) -
Jiang Tao,
Zhu Aisong,
Yang Chuqi,
Xu Chuyun,
Yang Danqian,
Lou Zhaohuan,
Zhang Guangji
Publication year - 2021
Publication title -
febs open bio
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.718
H-Index - 31
ISSN - 2211-5463
DOI - 10.1002/2211-5463.13089
Subject(s) - macrophage polarization , cyp2a6 , hepatocellular carcinoma , cytochrome p450 , arachidonic acid , cancer research , metastasis , inflammation , macrophage , chemistry , biology , medicine , enzyme , immunology , biochemistry , cancer , cyp1a2 , in vitro
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.