Abstract
Abstract
Histone deacetylases (HDACs) and lysine demethylases (KDMs) are key epigenetic enzymes regulating chromatin structure and gene transcription. Aberrant expression of those epigenetic modifiers has been extensively documented in cancer, but their role in hepatocellular carcinoma (HCC) is yet undefined. In this study, we aimed to analyze the expression of specific components of HDACs and KDMs in the liver tissue of HCC patients and evaluate the possible association with clinical outcome. Fifty-four patients with HCC of nonviral etiology were enrolled and followed-up for clinical and biochemical parameters after curative surgery. Gene expression of
HDAC11
,
KDM5D
,
KDM6B
, and
KDM8
was assessed in HCC tissues and homologous non-neoplastic liver tissues by RealTime q-PCR. For a subset of patients, total HDAC enzymatic activity in nuclear extracts from liver tissues was assessed.
HDAC11
was upregulated in 32 and downregulated in 19 HCC samples. In contrast,
KDMs
genes resulted mostly downregulated in HCC. Kaplan-Meier survival analysis revealed that patients with HDAC11 upregulation had a significantly higher mortality rate than those with
HDAC11
downregulation (
p
= 0.041). Furthermore, Cox regression analysis showed that
HDAC11
expression was a predictor of mortality with a hazard ratio (HR) of 2.29 (95% CI, 1.01–5.22;
p
= 0.04). This mortality risk even increased when adjusted for age, sex, C-reactive protein, creatinine, albumin, alpha fetoprotein, lipid parameters, microvascular invasion and tumor differentiation degree. These findings highlight a possible prognostic role for
HDAC11
in HCC and suggest to consider the potential of targeting histone-modifying enzymes for future therapeutic strategy.