The aim of this study was to investigate the genes associated with ferroptosis and the progression of hepatocellular carcinoma (HCC). The RNA sequencing data of erastin-induced ferroptosis in HCC cells were downloaded from the Sequence Read Archive database with accession number SRP119173. The microarray dataset GSE89377 of HCC progression was downloaded from the Gene Expression Omnibus database. The ferroptosis-related genes were screened by differential analysis and HCC progression-related genes were screened by cluster analysis using Mfuzz. Then, the genes associated with ferroptosis and HCC progression were screened by Venn analysis, followed by functional enrichment, protein–protein interaction (PPI) analysis, and transcription factor (TF) prediction. Finally, survival analysis was performed using data from the Cancer Genome Atlas database. A total of 33 upregulated and 52 downregulated genes associated with HCC progression and ferroptosis were obtained, and these genes were significantly involved in the negative regulation of ERK1 and ERK2 cascades; the NAD biosynthetic process; alanine, aspartate, and glutamate metabolism; and other pathways. The PPI network contained 52 genes and 78 interactions, of which, cell division cycle 20 (CDC20) and heat shock protein family B (small) member 1 (HSPB1) were hub genes found in higher degrees. Among the 85 genes associated with HCC progression and ferroptosis, two TFs (activating TF 3 (ATF3) and HLF) were predicted, with HSPB1 targeted by ATF3. In addition, 26 genes that were found to be significantly correlated with the overall survival of HCC patients were screened, including CDC20 and thyroid hormone receptor interactor 13. Several genes associated with HCC progression and ferroptosis were screened based on a comprehensive bioinformatics analysis. These genes played roles in HCC progression and ferroptosis via the negative regulation of the ERK1 and ERK2 cascades; the NAD biosynthetic process; and alanine, aspartate, and glutamate metabolism. ATF3 and HSPB1 played important roles in HCC progression and ferroptosis, with HSPB1 possibly regulated by ATF3.

本研究的目的是调查与铁死亡和肝细胞癌 (HCC) 进展相关的基因。从序列读取存档数据库下载erastin诱导的HCC细胞铁死亡的RNA测序数据，登录号为SRP119173。HCC 进展的微阵列数据集 GSE89377 从 Gene Expression Omnibus 数据库下载。通过差异分析筛选铁死亡相关基因，并使用Mfuzz通过聚类分析筛选HCC进展相关基因。然后，通过 Venn 分析筛选与铁死亡和 HCC 进展相关的基因，然后进行功能富集、蛋白质-蛋白质相互作用 (PPI) 分析和转录因子 (TF) 预测。最后，使用来自癌症基因组图谱数据库的数据进行生存分析。共获得了33个上调和52个下调与HCC进展和铁死亡相关的基因，这些基因显着参与了ERK1和ERK2级联的负调控；NAD生物合成过程；丙氨酸、天冬氨酸和谷氨酸代谢；和其他途径。PPI网络包含52个基因和78个相互作用，其中细胞分裂周期20（CDC20）和热休克蛋白家族B（小）成员1（HSPB1）是发现程度较高的枢纽基因。在与 HCC 进展和铁死亡相关的 85 个基因中，预测了两个 TF（激活 TF 3 (ATF3) 和 HLF），其中 HSPB1 被 ATF3 靶向。此外，还筛选了 26 个被发现与 HCC 患者总生存期显着相关的基因，包括 CDC20 和甲状腺激素受体相互作用因子 13。基于全面的生物信息学分析，筛选了与 HCC 进展和铁死亡相关的几个基因。这些基因通过 ERK1 和 ERK2 级联的负调控在 HCC 进展和铁死亡中发挥作用；NAD生物合成过程；以及丙氨酸、天冬氨酸和谷氨酸的代谢。ATF3 和 HSPB1 在 HCC 进展和铁死亡中起重要作用，其中 HSPB1 可能受 ATF3 调控。