Cancer Biomark. 2020;29(1):69-78. doi: 10.3233/CBM-190169.
Hepatocellular carcinoma (HCC) is the leading cause of mortality worldwide. In recent years, the incidence of HCC induced by NAFLD is growing rapidly.
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.
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.
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.
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.
肝细胞癌（HCC）是全球范围内导致死亡的主要原因。近年来，由非酒精性脂肪性肝病（NAFLD）引起的 HCC 的发病率迅速增长。
筛选出与 NAFLD 和 HCC 相关的新的致病基因和相关通路，并探讨从 NAFLD 进展为 HCC 的发病机制。
使用基因表达微阵列（GSE74656、GSE62232）鉴定差异表达基因（DEGs）。功能富集和通路富集分析表明，这些 DEGs 与细胞周期和细胞外外泌体有关，与 NAFLD 和 HCC 的发生发展密切相关。然后，我们使用搜索工具检索相互作用基因（STRING）来建立蛋白质-蛋白质相互作用（PPI）网络，并在 Cytoscape 中可视化它们。并对 TCGA 中的关键基因进行总体生存（OS）分析和基因表达验证。
共鉴定出 7 个关键基因，包括 CDK1、HSP90AA1、MAD2L1、PRKCD、ITGB3BP、CEP192 和 RHOB。最后，我们通过体外定量实时 PCR 验证了 ITGB3BP 和 CEP192 的表达水平。
本研究暗示了可能的差异表达基因，特别是新基因 CEP192，在 NAFLD 进展为 HCC 的过程中。需要进一步严格的实验来验证上述结果。
