Wu Dehai, Liao Guanqun, Yao Yuanfei, Huang Lining, Dong Bowen, Ma Yong, Yang Guangchao
Department of Hepatic Surgery, Second Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
Department of Hepatobiliary Surgery, Foshan Hospital Affiliated to Southern Medical University, Foshan, People's Republic of China.
J Hepatocell Carcinoma. 2023 Aug 9;10:1327-1339. doi: 10.2147/JHC.S418429. eCollection 2023.
The aim of this study is to explore the role of acetyl-CoA acyltransferase 2 (ACAA2) in the progression of hepatocellular carcinoma (HCC).
Bulk RNA data and single-cell RNA data were acquired from The Cancer Genome Atlas and Gene Expression Omnibus. Both in vitro and in vivo studies were used to determine the effect of ACAA2 on the progression of HCC, and RNA sequencing analysis was performed to explore the mechanism.
We found downregulation of ACAA2 was involved in the malignant progression of HCC. The patient with low ACAA2 level had an immunosuppressive microenvironment in the HCC and predicted to have a poor prognosis. Decreased ACAA2 facilitated HCC proliferation and metastasis by activating the nuclear factor-κB (NFκB) signaling pathway. And increased CXCL1 induced by NFκB signaling pathway might be responsible for low level of ACAA2 related immunosuppressive microenvironment. Furthermore, the expression of ACAA2 was also detected in immune cells. The expression of ACAA2 in CD4TCF7T, CD4FOXP3T, CD8GZMKT, and CD8KLRD1T cells was inversely correlated with the composition of CD8PDCD1T cells in HCC. This effect might be due to the CCL5-CCRs and HLA-E-KLRCs ligand-receptor networks.
In a conclusion, downregulated ACAA2 promoted the progression of hepatocellular carcinoma and might be participated in the formation of immunosuppressive microenvironment. ACAA2 could be served as a favorable indicator for the prognosis of HCC and an ideal biomarker for immunotherapy.
本研究旨在探讨乙酰辅酶A酰基转移酶2（ACAA2）在肝细胞癌（HCC）进展中的作用。
从癌症基因组图谱和基因表达综合数据库获取批量RNA数据和单细胞RNA数据。采用体外和体内研究来确定ACAA2对HCC进展的影响，并进行RNA测序分析以探索其机制。
我们发现ACAA2的下调参与了HCC的恶性进展。ACAA2水平低的患者在HCC中具有免疫抑制微环境，且预后较差。ACAA2的降低通过激活核因子κB（NFκB）信号通路促进HCC的增殖和转移。NFκB信号通路诱导的CXCL1增加可能是ACAA2相关免疫抑制微环境水平低的原因。此外，还在免疫细胞中检测到了ACAA2的表达。HCC中CD4TCF7T、CD4FOXP3T、CD8GZMKT和CD8KLRD1T细胞中ACAA2的表达与CD8PDCD1T细胞的组成呈负相关。这种效应可能归因于CCL5-CCRs和HLA-E-KLRCs配体-受体网络。
总之，ACAA2下调促进肝细胞癌进展，并可能参与免疫抑制微环境的形成。ACAA2可作为HCC预后的良好指标和免疫治疗的理想生物标志物。
