Clinical and Translational Medicine (Mar 2021)

Quantitative acetylome analysis reveals histone modifications that may predict prognosis in hepatitis B‐related hepatocellular carcinoma

  • Xiaoqiang Chai,
  • Jianfei Guo,
  • Ruizhao Dong,
  • Xuan Yang,
  • Chao Deng,
  • Chuanyuan Wei,
  • JiaJie Xu,
  • Weiyu Han,
  • Jiacheng Lu,
  • Chao Gao,
  • Dongmei Gao,
  • Cheng Huang,
  • Aiwu Ke,
  • Shuangqi Li,
  • Huanping Li,
  • Yingming Tian,
  • Zhongkai Gu,
  • Shuxian Liu,
  • Hang Liu,
  • Qilong Chen,
  • Feng Liu,
  • Jian Zhou,
  • Jia Fan,
  • Guoming Shi,
  • Feizhen Wu,
  • Jiabin Cai

DOI
https://doi.org/10.1002/ctm2.313
Journal volume & issue
Vol. 11, no. 3
pp. n/a – n/a

Abstract

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Abstract Lysine acetylation (Kac) as an important posttranslational modification of histones is essential for the regulation of gene expression in hepatocellular carcinoma (HCC). However, the atlas of whole acetylated proteins in HCC tissues and the difference in protein acetylation between normal human tissues and HCC tissues are unknown. In this report, we characterized the proteome and acetyl proteome (acetylome) profile of normal, paracancerous, and HCC liver tissues in human clinical samples by quantitative proteomics techniques. We identified 6781 acetylation sites of 2582 proteins and quantified 2492 acetylation sites of 1190 proteins in normal, paracancerous, and HCC liver tissues. Among them, 15 proteins were multiacetylated with more than 10 lysine residues. The histone acetyltransferases p300 and CBP were found to be hyperacetylated in hepatitis B virus pathway. Moreover, we found that 250 Kac sites of 214 proteins were upregulated and 662 Kac sites of 451 proteins were downregulated in HCC compared with normal liver tissues. Additionally, the acetylation levels of lysine 120 in histone H2B (H2BK120ac), lysine 18 in histone H3.3 (H3.3K18ac), and lysine 77 in histone H4 (H4K77ac) were increased in HCC. Interestingly, the higher levels of H2BK120ac, H3.3K18ac, and H4K77ac were significantly associated with worse prognosis, such as poorer survival and higher recurrence in an independent clinical cohort of HCC patients. Overall, this study lays a foundation for understanding the functions of acetylation in HCC and provides potential prognostic factors for the diagnosis and therapy of HCC.

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