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

Aging (Albany NY). 2018 Aug 20;10(8):2079-2097. doi: 10.18632/aging.101531.

Abstract

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.

Keywords: AKR1B10; Copy Number Variants; Hepatocellular Carcinoma; aging; gene mutation; m RNA expression.

MeSH terms

  • Adolescent
  • Aged, 80 and over
  • Aging / physiology*
  • Aldehyde Reductase / genetics
  • Aldehyde Reductase / metabolism
  • Aldo-Keto Reductases
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Child
  • DNA Copy Number Variations
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Female
  • Genetic Predisposition to Disease
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • RNA, Messenger
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism
  • Young Adult
  • beta Catenin / genetics
  • beta Catenin / metabolism

Substances

  • CTNNB1 protein, human
  • DNA-Binding Proteins
  • KMT2D protein, human
  • Neoplasm Proteins
  • RNA, Messenger
  • Tumor Suppressor Protein p53
  • beta Catenin
  • AKR1B10 protein, human
  • Aldo-Keto Reductases
  • Aldehyde Reductase