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Research Paper|Volume 14, Issue 19|pp 7926—7940

Identification of ACSF gene family as therapeutic targets and immune-associated biomarkers in hepatocellular carcinoma

Zijin Zhao1,2, Miaomiao Liu3, Zhijie Xu4,5,6, Yuan Cai4, Bi Peng4, Qiuju Liang7, Yuanliang Yan7, Wei Liu4, Fanhua Kang5, Qingchun He8, Qianhui Hong5, Wenqin Zhang5, Jianbo Li5, Jinwu Peng4,5, Shuangshuang Zeng7
  • 1Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China
  • 2Clinical Research Center for Skull Base Surgery and Neuro-Oncology in Hunan Province, Changsha, China
  • 3Department of Nuclear Medicine (PET-CT Central), Xiangya Hospital, Central South University, Changsha, China
  • 4Department of Pathology, Xiangya Hospital, Central South University, Changsha, China
  • 5Department of Pathology, Xiangya Changde Hospital, Changde, Hunan, China
  • 6National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China
  • 7Department of Pharmacy, Xiangya Hospital, Central South University, Changsha, China
  • 8Department of Emergency, Xiangya Hospital, Central South University, Changsha, Hunan, China
Received: February 18, 2022Accepted: September 23, 2022Published: October 4, 2022
https://doi.org/10.18632/aging.204323

Copyright: © 2022 Zhao et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Acyl-CoA synthetases (ACSs) are responsible for acyl-CoA synthesis from nonpolar hydrophilic fatty acids and play a vital role in many metabolic processes. As a category of ACS isozymes, members of ACS family (AACS, ACSF2-3, AASDH) participate in lipid metabolism; however, their expression patterns, regulatory mechanisms and effects in hepatocellular carcinoma (HCC) are poorly understood. Here, through evaluating the expression profiles of ACSF gene family, we found that upregulated AACS might be more significant and valuable in development and progression of HCC. Consequently, the mRNA expression levels of AACS and ACSF2 was accordantly increased in HCC. Kaplan-Meier plotter revealed that HCC patients with high level of AACS were highly related to a shorter overall survival time and relapse-free survival. Genetic alterations using cBioPortal revealed that the alteration rate of AACS were 5%. We also found that the functions of ACSF gene family were linked to several cancer-associated pathways, including long-term potentiation, phospholipase D signaling pathway and purine metabolism. TIMER database indicated that the AACS and ACSF2 had a strong relationship with the infiltration of six types of immune cells (macrophages, neutrophils, CD8+ T-cells, B-cells, CD4+ T-cells and dendritic cells). Next, Diseasemeth database revealed that the global methylation levels of ACSF2 was higher in HCC patients. In conclusion, this study firstly demonstrated that Acyl-CoA synthesis gene family, in particular, AACS, could be associated with immune microenvironment, thereby influencing the development and prognosis of patients with HCC.