Research Paper Volume 10, Issue 8 pp 2079—2097

Integrated analysis of the impact of age on genetic and clinical aspects of hepatocellular carcinoma

Manar Atyah1,2, *,, Yi-Rui Yin1,2, *,, Chen-Hao Zhou1,2, , Qiang Zhou1,2, , Wan-Yong Chen1,2,3,4, , Qiong-Zhu Dong4,5, , Ning Ren1,2,3,4, ,

  • 1 Department of Liver Surgery and Transplantation, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai 200032, China
  • 2 Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai 200032, China
  • 3 Department of Surgery, Minhang Branch, Zhongshan Hospital, Fudan University, Shanghai 201199, China
  • 4 Institute of Fudan-Minhang Academic Health System, Minhang Hospital, Fudan University, Shanghai 201199, China
  • 5 Institutes of Biomedical Sciences, Fudan University, Shanghai 200032, China
* Equal contribution

Received: June 5, 2018       Accepted: August 13, 2018       Published: August 20, 2018
How to Cite

Copyright: Atyah 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.


Despite the rapid growing and aging of populations worldwide, our knowledge on hepatocellular carcinoma (HCC) is still age-standardized rather than age-specific, with only few studies exploring the topic from a genetic point of view. Here, we analyze clinical and genetic aspects of HCC in patients of different age groups with the major attention directed to children (≤20 y) and elderly groups (≥80 y). A number of significant differences were found in elderly patients compared to children group, including smaller tumor size (P=0.001) and improved survival rates (P=0.002). Differences in gene mutations, copy number variants, and mRNA expressions were identified between the groups, with alteration rates for some genes like AKR1B10 increasing significantly with the age of patients. Immunohistochemistry testing of AKR1B10 showed a significant difference in expression levels at the age of 40 (30.77% high expression rate in patients younger than 40 compared to 51.57% in older patients) (P=0.043). Expression levels also differed between HCC tissues (49.64%) and near-tumor tissues (6.58%) (P<0.001). These findings contribute to the limited data available regarding the age-specific aspects of HCC patients, and support the need to address potential differences in the diagnosis, treatment, and prevention strategies of HCC.


HCC: Hepatocellular Carcinoma, HBV: Hepatitis B Virus, HCV: Hepatitis C Virus, AFB1: Aflatoxin B1, NSAIDs: Non-steroidal Anti-inflammatory Drugs, AFB: α-Fetoprotein, DCP: Des-γ-carboxyprothrombin, CNVs: Copy Number Variants, OS: Overall Survival, DFS: Disease Free Survival, AKR: Aldo-Keto Reductase, NADP: Nicotinamide Adenine Dinucleotide Phosphate, IHC: Immunohistochemistry, Nrf2: nuclear factor erythroid 2-related factor, ROS: Reactive Oxygen Species, RNS: Reactive Nitrogen Species.