蜘蛛烯酸代谢的CYP450途径在肝细胞癌中被破坏,并与微血管浸润有关。
Arachidonic acid metabolism CYP450 pathway is deregulated in hepatocellular carcinoma and associated with microvascular invasion.
发表日期:2023 Sep 01
作者:
Kai Wang, Ji-Hua Shi, Jie Gao, Yaohui Sun, Zhihui Wang, Xiaoyi Shi, Wenzhi Guo, Yang Jin, Shuijun Zhang
来源:
GENES & DEVELOPMENT
摘要:
花生四烯酸代谢在炎症和代谢性肝病的发展和进展中起着至关重要的作用。然而,它在肝细胞癌(HCC)中的作用尚不清楚。本研究利用生物信息学、蛋白质组学和免疫组化分析的组合,调查了参与花生四烯酸代谢途径的关键基因在HCC中的表达。通过对公开可得的数据集、临床HCC组织和组织芯片阵列的全面分析,我们比较了肝花生四烯酸代谢基因的表达。我们观察到HCC组织中细胞色素P450(CYP450)途径基因的信使RNA和蛋白质水平均显著下调,与正常肝组织相比。此外,我们观察到花生四烯酸代谢CYP450途径的失调与HCC的病理特征和预后之间存在强相关性。具体而言,CYP2C8/9/18/19的表达与病理等级(r = -0.484,p < 0.0001)、血管侵袭(r = -0.402,p < 0.0001)、天门冬氨酸转氨酶(r = -0.246, p = 0.025)、γ-谷氨酰转肽酶(r = -0.252, p = 0.022)、碱性磷酸酶(r = -0.342, p = 0.002)、α-胎蛋白(r = -0.311, p = 0.004)和糖类抗原19-9(r = -0.227, p = 0.047)显著相关。此外,我们发现CYP450途径活性与HCC的血管侵袭之间存在显著关联。总之,这些数据表明,花生四烯酸CYP450代谢途径的紊乱与HCC的进展相关,并可能成为HCC患者早期复发的潜在预测因子。© 2023国际细胞生物学联合会
Arachidonic acid metabolism plays a crucial role in the development and progression of inflammatory and metabolic liver diseases. However, its role in hepatocellular carcinoma (HCC) remains unclear. In this study, we investigated the expression of key genes involved in the arachidonic acid metabolism pathway in HCC using a combination of bioinformatics, proteomics and immunohistochemistry analyses. Through a comprehensive analysis of publicly available datasets, clinical HCC tissues, and tissue microarrays, we compared the expression of hepatic arachidonic acid metabolic genes. We observed significant downregulation of cytochrome P450 (CYP450) pathway genes at both the messenger RNA and protein levels in HCC tissues compared to normal liver tissues. Furthermore, we observed a strong correlation between the deregulation of the arachidonic acid metabolism CYP450 pathway and the pathological features and prognosis of HCC. Specifically, the expression of CYP2C8/9/18/19 was significantly correlated with pathological grade (r = -.484, p < .0001), vascular invasion (r = -.402, p < .0001), aspartate transaminase (r = -.246, p = .025), gamma-glutamyl transpeptidase (r = -.252, p = .022), alkaline phosphatase (r = -.342, p = .002), alpha-fetoprotein (r = -.311, p = .004) and carbohydrate antigen 19-9 (r = -.227, p = .047). Moreover, we discovered a significant association between CYP450 pathway activity and vascular invasion in HCC. Collectively, these data indicate that arachidonic acid CYP450 metabolic pathway deregulation is implicated in HCC progression and may be a potential predictive factor for early recurrence in patients with HCC.© 2023 International Federation of Cell Biology.