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. 2020;29(1):69-78.
doi: 10.3233/CBM-190169.

Identification of genes in hepatocellular carcinoma induced by non-alcoholic fatty liver disease

Changzhou Cai, Xin Song, Chaohui Yu

Identification of genes in hepatocellular carcinoma induced by non-alcoholic fatty liver disease

Changzhou Cai et al. Cancer Biomark. 2020.

Abstract

Background: Hepatocellular carcinoma (HCC) is the leading cause of mortality worldwide. In recent years, the incidence of HCC induced by NAFLD is growing rapidly.

Objective: To screen for new pathogenic genes and related pathways both in NAFLD and HCC, and to explore the pathogenesis of progression from NAFLD to HCC.

Methods: Gene expression microarrays (GSE74656, GSE62232) were used for identifying differentially expressed genes (DEGs). Functional enrichment and pathway enrichment analyses indicated that these DEGs were related to cell cycle and extracellular exosome, which were closely related to NAFLD and HCC development. We then used the Search Tool for the Retrieval of Interacting Genes (STRING) to establish the protein-protein interaction (PPI) network and visualized them in Cytoscape. And the overall survival (OS) analysis and gene expression validation in TCGA of hub genes was performed.

Results: Seven hub genes, including CDK1, HSP90AA1, MAD2L1, PRKCD, ITGB3BP, CEP192, and RHOB were identified. Finally, we verified the expression level of ITGB3BP and CEP192 by quantitative real-time PCR in vitro.

Conclusions: The present study implied possible DEGs, especially the new gene CEP192, in the progression of NAFLD developing to HCC. Further rigorous experiments are required to verify the above results.

Keywords: CEP192; Expression; bioinformatics; hepatocellular carcinoma; non-alcoholic fatty liver disease.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Figure 1.
Figure 1.
Identification of differentially expressed genes in mRNA expression profiling datasets (GSE24807, GSE62232). (A) High expression gens; (B) Low expression genes.
Figure 2.
Figure 2.
Protein-protein interaction (PPI) network and core modules of PPI network. (A) High and low expression genes; (B) Core modules. The pink circles represent high expression genes, and the blue circles represent low expression genes.
Figure 3.
Figure 3.
Overall survivals of significant hub genes selected from aberrantly methylated-DEGs. Hub genes included CDK1, HSP90AA1, EHMT2, MAD2L1, COL1A1, PRKCD, NPL, PAK1, RHOC, COL1A2, ITGB3BP, CASC5, CEP192, TUBGCP6, RHOB and MCL1. P< 0.05 was considered statistically significant.
Figure 4.
Figure 4.
Gene expression statuses of 8 hub genes were validated in TCGA database. The results are expressed as the mean ± SD of 50 paired HCC samples and adjacent normal liver samples. p*< 0.05, p**< 0.01, p*⁣**< 0.001, p*⁣*⁣**⁢ï⁢¼⁢ 0.0001.
Figure 5.
Figure 5.
Gene expression status of CEP192 and ITGB3BP were validated by qRT-PCR. (A, C) The expression of CEP192 and ITGB3BP in 4 human HCC cells (HepG2, Hep3B, Huh7 and LM3) and 2 normal human hepatic cells (QSG-7701 and L-02); (B, D) The expression of CEP192 and ITGB3BP in PA-treated cells (QSG-7701 and L-02) and normal controls. The results are expressed as the mean ± SD. p*< 0.05, p**< 0.01.
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