Identification of key genes and important histone modifications in hepatocellular carcinoma

Yu-Xian Liu; Qian-Zhong Li; Yan-Ni Cao; Lu-Qiang Zhang

doi:10.1016/j.csbj.2020.09.013

Identification of key genes and important histone modifications in hepatocellular carcinoma

Comput Struct Biotechnol J. 2020 Sep 20:18:2657-2669. doi: 10.1016/j.csbj.2020.09.013. eCollection 2020.

Authors

Yu-Xian Liu¹, Qian-Zhong Li^{1

2}, Yan-Ni Cao¹, Lu-Qiang Zhang¹

Affiliations

¹ Laboratory of Theoretical Biophysics, School of Physical Science and Technology, Inner Mongolia University, Hohhot 010021, China.
² The State Key Laboratory of Reproductive Regulation and Breeding of Grassland Livestock, Inner Mongolia University, Hohhot 010070, China.

Abstract

Hepatocellular carcinoma (HCC) is one of the leading causes of cancer death in the world. It has been reported that HCC is closely related to the changes of histone modifications. However, finding histone modification patterns in key genes which related to HCC is still an important task. In our study, the patterns of 11 kinds of histone modifications in the promoter regions for the different types of genes were analyzed by hierarchical screening for hepatocyte (normal) cell line and HepG2 (tumor) cell line. The important histone modifications and their key modification regions in different types of genes were found. The results indicate that these important genes may play a pivotal role in the occurrence of HCC. By analyzing the differences of histone modifications and gene expression levels for these important genes between the two cell lines, we found that the signals of H3K4me3, H3K27ac, H3K9ac, and H3K4me2 in HCC are significantly stronger. The changed regions of important histone modifications in 17 key genes were also identified. For example, the H3K4me3 signals increased 150 times in regions (-1500, -500) bp and (0, 1000) bp of ARHGAP5 in tumor cell line than in normal cell line. Finally, a prognostic risk scoring model was constructed, and the effects of key genes on the prognosis of HCC were verified by the survival analysis. Our results may provide a more precise potential therapeutic targets for identifying key genes and histone modifications in HCC as new biomarkers.

Keywords: Biomarkers; DHLEG, Different highly and lowly expressed genes; Gene expression; H2AFZ, H2A histone family member Z; H3K27ac, Histone H3 acetylated at lysine 27; H3K27me3, Histone H3 trimethylated at lysine 27; H3K36me3, Histone H3 trimethylated at lysine 36; H3K4me1, Histone H3 monomethylated at lysine 4; H3K4me2, Histone H3 dimethylated at lysine 4; H3K4me3, Histone H3 trimethylated at lysine 4; H3K79me2, Histone H3 dimethylated at lysine 79; H3K9ac, Histone H3 acetylated at lysine 9; H3K9me3, Histone H3 trimethylated at lysine 9; H4K20me1, Histone H4 monomethylated at lysine 20; HCC, Hepatocellular carcinoma; Histone modification signals; NH, The genes are highly expressed in normal cell line but not in tumor cell line; NH-TL, The genes are highly expressed in normal cell line and lowly expressed in tumor cell line; NL, The genes are lowly expressed in normal cell line but not in tumor cell line; NL-TH, The genes are lowly expressed in normal cell line and highly expressed in tumor cell line; ONCO, Oncogenes; Oncogenes; TH, The genes are highly expressed in tumor cell line but not in normal cell line; TL, The genes are lowly expressed in tumor cell line but not in normal cell line; TSG, Tumor suppressor genes; Tumor suppressor genes.