Investigating Pathogenic and Hepatocarcinogenic Mechanisms from Normal Liver to HCC by Constructing Genetic and Epigenetic Networks via Big Genetic and Epigenetic Data Mining and Genome-Wide NGS Data Identification

Abstract

The prevalence of hepatocellular carcinoma (HCC) is still high worldwide because liver diseases could develop into HCC. Recent reports indicate nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NAFLD&NASH) and primary biliary cirrhosis and primary sclerosing cholangitis (PBC&PSC) are significant of HCC. Therefore, understanding the cellular mechanisms of the pathogenesis and hepatocarcinogenesis from normal liver cells to HCC through NAFLD&NASH or PBC&PSC is a priority to prevent the progression of liver damage and reduce the risk of further complications. By the genetic and epigenetic data mining and the system identification through next-generation sequencing data and its corresponding DNA methylation profiles of liver cells in normal, NAFLD&NASH, PBC&PSC, and HCC patients, we identified the genome-wide real genetic and epigenetic networks (GENs) of normal, NAFLD&NASH, PBC&PSC, and HCC patients. In order to get valuable insight into these identified genome-wide GENs, we then applied a principal network projection method to extract the corresponding core GENs for normal liver cells, NAFLD&NASH, PBC&PSC, and HCC. By comparing the signal transduction pathways involved in the identified core GENs, we found that the hepatocarcinogenesis through NAFLD&NASH was induced through DNA methylation of HIST2H2BE, HSPB1, RPL30, and ALDOB and the regulation of miR-21 and miR-122, and the hepatocarcinogenesis through PBC&PSC was induced through DNA methylation of RPL23A, HIST2H2BE, TIMP1, IGF2, RPL30, and ALDOB and the regulation of miR-29a, miR-21, and miR-122. The genetic and epigenetic changes in the pathogenesis and hepatocarcinogenesis potentially serve as potential diagnostic biomarkers and/or therapeutic targets.

High Levels of HIST1H2BK in Low-Grade Glioma Predicts Poor Prognosis: A Study Using CGGA and TCGA Data

“…Finally, co-expression analysis showed that HIST1H2BK was positively associated with HIST1H2AG, HIST2H2AA4, HIST1H2BJ, HIST2H2BE, and HIST1H2AC, and was negatively associated with PDZD4, CRY2, GABBR1, RP5-1119A7.17, and KCNJ11. As previously reported, HIST2H2BE may be a promising drug target that could mitigate autoimmune deficiency (40). Moreover, co-immunoprecipitation of HNRNP-K with SERPINA3 correlated with levels of HIST2H2BE transcripts and telomere length in hepatocellular carcinoma (HCC) tissues (41).…”

Identification of crucial genes and pathways associated with prostate cancer in multiple databases

“… 47 Moreover, methylation of RPL30 downregulated the dysfunction of anti-apoptosis that is involved in non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) pathways, which could lead to hepatocarcinogenesis. 48 In head and neck squamous cell carcinoma, RPL30 and other genes 49 were determined as the internal core genes with stable expression. SEC61A1 , as a hallmark DNA repair gene, was identified as a potential independent indicator of prognosis in hepatocellular carcinoma in a gene-wide association study.…”

Potential Role of NEU1 in Hepatocellular Carcinoma: A Study Based on Comprehensive Bioinformatical Analysis

“…In addition, the 5-year survival rates of HCC ranges from 3 to 28%. (Li et al, 2018). Most patients with HCC are at intermediate or advanced stages when diagnosed and are not suitable for surgical treatment (Wu et al, 2020a).…”