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

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.

Diagnostic and Prognostic Potential of AKR1B10 in Human Hepatocellular Carcinoma

“…In that work, the authors also showed that AKR1B10 knockdown in vitro corresponded with increased apoptotic cell death, decreased colony formation and size, and improved response to doxorubicin. In an analysis involving children and older adults (≥80 years), AKR1B10 protein levels differed between HCC tissues and near-tumor tissues for HCC patients [27]. Interestingly, this study also revealed a significant difference in AKR1B10 expression according to age, with increased expression in older patients compared to levels in patients younger than 40 years.…”

Identification of Aging-Related Genes Associated With Clinical and Prognostic Features of Hepatocellular Carcinoma

“…Aging is associated with impaired immunological function and an accumulated chronic inflammatory microenvironment, which might facilitate tumor formation and progression (Kuilman et al, 2008 ). Recently, a retrospective study found that elderly patients exhibited better biological characteristics than children, but the underlying mechanisms for this observation remain unknown (Atyah et al, 2018 ). AKR1B10, which plays an important role in the adoptive response to oxidative stress and damage and is considered to be involved in leading theories of aging, was identified as a crucial gene in the increase of carcinogenesis with age (Schmitz et al, 2011 ; Sato et al, 2016 ).…”

“…Interestingly, a latest retrospective study of 131 HCC patients (98 elderly patients and 33 children) reported that patients aged >85 years had smaller tumors compared with children, and that their survival rate was 92.4%, which was comparable with that of patients aged ≤ 85 years and was significantly higher than that of the children (Atyah et al, 2018 ). AKR1B10, which is involved in leading theories on aging, has also been identified as a crucial gene in the increase of carcinogenesis with age (Matkowskyj et al, 2014 ; Atyah et al, 2018 ). However, to our best knowledge, the role of the aging process in HCC remains unclear, and the correlation between aging genes and HCC prognosis has not yet been systematically evaluated.…”

Association of Age With Tumor Grade in Patients With Digestive Tumors: A Study Based on US SEER&nbsp;Registry

“…[14] Puccini, et al showed a signi cantly different mutation rates between younger and older patients in colorectal cancer. [15] Atyah, et al also observed differencesin gene mutations, copy number variants, and mRNA expressions in older and younger patients with hepatocellular carcinoma [14]. However, further studies are still needed to illustrate the mechanisms behind the phenomena observed in this study.…”