Research Paper Volume 12, Issue 5 pp 4573—4591

APEX1 is a novel diagnostic and prognostic biomarker for hepatocellular carcinoma

Lei Cao1,2,3, *, , Hongwei Cheng4, *, , Qiuxia Jiang5, , Hui Li3, , Zhixian Wu1,2, ,

  • 1 Department of Hepatobiliary Disease, Dongfang Hospital, Xiamen University, Fuzhou, China
  • 2 The 900th Hospital of the People’s Liberation Army Joint Service Support Force, Fuzhou, China
  • 3 Department of Pathology, Quanzhou Women's and Children's Hospital, Quanzhou, China
  • 4 Institute of Chinese Medical Sciences, University of Macau, Macau SAR, China
  • 5 Department of Ultrasound, Quanzhou Women’s and Children’s Hospital, Quanzhou, China
* Equal contribution

Received: September 18, 2019       Accepted: March 2, 2020       Published: March 13, 2020
How to Cite

Copyright © 2020 Cao 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.


In this study, we analyzed the expression and clinical significance of apyrimidinic endodeoxyribonuclease 1 (APEX1) in hepatocellular carcinoma (HCC). The APEX1 mRNA and protein levels were significantly higher in HCC than adjacent normal liver tissues in multiple datasets from the Oncomine, GEO and TCGA databases. APEX1 levels were significantly higher in early-stage HCC patients with low alpha-fetoprotein expression. The positive predictive value (PPV) for APEX1 was significantly higher than the PPV for alpha-fetoprotein (67.91% vs. 55.22%) in HCC patients. High APEX1 expression correlated with resistance to sorafenib and anti-programmed death 1 (PD-1) therapies in HCC patients, and it associated with poorer overall survival, disease-specific survival, progression-free survival, and relapse-free survival in early- and advanced-stage HCC patients. High APEX1 expression also associated with poor prognosis in non-alcoholic, vascular invasion-negative, and hepatitis virus-negative HCC patients. These data suggest that APEX1 is a better diagnostic and prognostic biomarker than alpha-fetoprotein in HCC. Gene set enrichment analysis (GSEA) showed that APEX1 expression correlated with the DNA damage repair pathway in HCC tissues. These findings demonstrate that APEX1 is a potential diagnostic and prognostic biomarker in HCC.


APEX1: apyrimidinic endodeoxyribonuclease 1; HCC: hepatocellular carcinoma; HBV: hepatitis B virus; HCV: hepatitis C virus; AFP: alpha-fetoprotein; GPC3: glypican 3; GP73: golgi protein-73; DCP: descarboxyprothrombin; GPT: glutamic-pyruvic transaminase; GGCX: gamma-glutamyl carboxylase; OS: overall survival; DSS: disease-specific survival; PFS: progression-free survival; PPV: predictive value; NPV: negative predictive value; AUC: area under the curve; PD-1: programmed death 1.