肝动脉化疗栓塞（TACE）是中期肝细胞癌（HCC）的标准治疗方法。然而，很大一部分患者对 TACE 无反应或反应较差。因此，我们的目标是确定 TACE 应答者或非应答者的目标。 GSE104580 用于识别 TACE 应答者和非应答者中的差异表达基因 (DEG)。在蛋白质-蛋白质相互作用 (PPI) 分析之后，使用 Cytoscape 软件中的 MCC 和 MCODE 插件以及 LASSO 回归分析来识别枢纽基因。进行基因集富集分析（GSEA）来研究潜在的机制。随后，使用癌症基因组图谱 (TCGA)、癌细胞系百科全书 (CCLE) 和人类蛋白质图谱 (HPA) 数据库的数据验证了中心基因。为了评估中心基因的临床意义，采用了 Kaplan-Meier (KM) 生存和 Cox 回归分析。共鉴定出375个DEG，PPI分析后剩余126个，通过多重筛选方法最终确定TTK（一种与细胞增殖相关的双特异性蛋白激酶）为枢纽基因。 TCGA、CCLE 和 HPA 数据库的数据分析显示 HCC 组织中 TTK 表达升高。 GSEA 表明细胞周期、法尼醇 X 受体通路、PPAR 通路、FOXM1 通路、E2F 通路和铁死亡可能是 TACE 无反应者的潜在机制。免疫细胞浸润分析显示 TTK 和 Th2 细胞之间存在显着相关性。 KM和Cox分析提示TTK高表达的HCC患者预后较差。 TTK 可能在 HCC 患者对 TACE 治疗的反应中发挥关键作用，并可能与这些患者的预后相关。© 2024。作者获得 Springer Science Business Media, LLC（Springer Nature 旗下子公司）的独家许可。

Transhepatic arterial chemoembolization (TACE) is the standard treatment for intermediate-stage hepatocellular carcinoma (HCC). However, a significant proportion of patients are non-responders or poor responders to TACE. Therefore, our aim is to identify the targets of TACE responders or non-responders. GSE104580 was utilized to identify differentially expressed genes (DEGs) in TACE responders and non-responders. Following the protein-protein interaction (PPI) analysis, hub genes were identified using the MCC and MCODE plugins in Cytoscape software, as well as LASSO regression analysis. Gene set enrichment analysis (GSEA) was performed to investigate potential mechanisms. Subsequently, the hub genes were validated using data from The Cancer Genome Atlas (TCGA), the Cancer Cell Line Encyclopedia (CCLE), and The Human Protein Atlas (HPA) database. To evaluate the clinical significance of the hub genes, Kaplan-Meier (KM) survival and Cox regression analysis were employed. A total of 375 DEGs were identified, with 126 remaining following PPI analysis, and TTK, a dual-specificity protein kinase associated with cell proliferation, was ultimately identified as the hub gene through multiple screening methods. Data analysis from TCGA, CCLE, and HPA databases revealed elevated TTK expression in HCC tissues. GSEA indicated that the cell cycle, farnesoid X receptor pathway, PPAR pathway, FOXM1 pathway, E2F pathway, and ferroptosis could be potential mechanisms for TACE non-responders. Analysis of immune cell infiltration showed a significant correlation between TTK and Th2 cells. KM and Cox analysis suggested that HCC patients with high TTK expression had a worse prognosis. TTK may play a pivotal role in HCC patients' response to TACE therapy and could be linked to the prognosis of these patients.© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.