由于肥胖、2型糖尿病和非酒精性脂肪肝病（NAFLD）正在取代病毒和酒精引起的肝病成为主要的致病因素，肝细胞肝癌（HCC）的负担在稳步增加。本研究旨在利用综合生物信息学分析识别非酒精性脂肪性肝炎（NASH）诱导的HCC发展的关键基因和通路。下载了两个基因表达谱数据集GSE102079和GSE164760。筛选了来自HCC和健康对照样本的差异表达基因（DEGs）。基于Gene Ontology（GO）资源和Kyoto Encyclopedia of Genes and Genomes（KEGG）资源进行功能富集分析。然后使用Cytoscape和Search Tool for the Retrieval of Interacting Genes（STRING）可视化这些DEGs的蛋白质相互作用（PPI）。利用GEPIA2、UALCAN、GSCA和TIMER2.0数据库探索了关键基因的表达和生存分析、甲基化和遗传突变分析。我们从这两个数据集中识别出158个重叠基因。上调基因主要与肿瘤的增殖、粘附和转移有关，而下调基因主要与氧化应激和能量代谢有关。CDKN2A、SPP1、CYP2C9和CYP4A11与预后表现相关，被认为是潜在的关键基因，其中SPP1、CYP2C9和CYP4A11被识别为甲基化驱动的基因。在HCC的不同突变状态下，CDKN2A、SPP1、CYP2C9和CYP4A11的基因表达显示出显著差异。CDKN2A和SPP1被识别为风险基因，而CYP2C9和CYP4A11被识别为保护基因，可能影响NASH向HCC的转化过程。

The burden of hepatocellular carcinoma (HCC) is steadily growing because obesity, type 2 diabetes, and nonalcoholic fatty liver disease (NAFLD) are replacing viral- and alcohol-related liver disease as major pathogenic promoters. The current study attempted to identify the key genes and pathways in the non-alcoholic steatohepatitis (NASH) induced development of HCC using integrated bioinformatics analyses. Two gene expression profiling datasets, GSE102079 and GSE164760 were downloaded. Differentially expressed genes (DEGs) from HCC and healthy control samples were screened. Functional enrichment analyses based on Gene Ontology (GO) resource, Kyoto Encyclopedia of Genes and Genomes (KEGG) resource. Then protein-protein interaction (PPI) of these DEGs was visualized by Cytoscape with Search Tool for the Retrieval of Interacting Genes (STRING). Expression and survival analysis of hub genes, methylation and genetic mutation analysis were explored with GEPIA2, UALCAN, GSCA, and TIMER2.0 databases. We identified 158 overlapping genes from the 2 datasets. Up-regulated genes were mainly related to the proliferation, adhesion and metastasis of tumors, while down-regulated genes were mainly related to oxidative stress and energy metabolism. CDKN2A, SPP1, CYP2C9 and CYP4A11 were associated with prognostic performance and were considered the potential crucial genes, which SPP1, CYP2C9 and CYP4A11 were identified as the DNA methylation-driven genes. In different mutation statuses of HCC, gene expression of CDKN2A, SPP1, CYP2C9 and CYP4A11 showed significant differences. CDKN2A and SPP1 were identified as risk genes, while CYP2C9 and CYP4A11 were identified as protective genes, which may affect the transformation of NASH into HCC.