Li Tongfei, Liu Shujuan, Wang Shengjun, Sun Shan, Ji Feng, Li Mingliang, Zhang Yong
Department of Interventional Radiology, The Second Affiliated Hospital of Shandong First Medical University, Tai'an, 271000, China.
Department of Oncology, Jinan Seventh People's Hospital, Jinan, 250132, China.
Discov Oncol. 2025 May 22;16(1):861. doi: 10.1007/s12672-025-02606-z.
Metabolic reprogramming plays an important role in therapeutic efficacy of hepatocellular carcinoma (HCC). However, the metabolic reprogramming-related key genes associated with transcatheter arterial chemoembolization (TACE) treatment sensitivity in HCC remain further investigation.
We analyzed data from public databases, The Cancer Genome Atlas and Gene Expression Omnibus, as well as metabolism-related genes (MRGs), to identify key genes associated with TACE treatment sensitivity. Further analysis was conducted on the relationship between key genes and immune cell infiltration, HCC-related genes, regulatory network construction, nomogram construction, and drug sensitivity analysis. Finally, the expression of key genes was validated based on databases and in vitro RT-qPCR.
Four key genes (CDC20, LPCAT1, PON1, and SPP1) associated with TACE treatment sensitivity were identified. Increased CDC20, LPCAT1, and SPP1 and reduced PON1 were found in tumor tissues than normal tissues, as well as in advanced patients than early-stage patients. Lower expression of CDC20, LPCAT1, and SPP1, and higher expression of PON1 were detected in responsive patients than non-responsive patients. Patients with high expression of CDC20, LPCAT1, and SPP1, and low expression of PON1 had poor prognosis. They were also correlated with tumor immune microenvironment and sensitivity to multiple chemotherapy drugs. The expressions of key genes at the gene and protein levels were validated.
Our study provided systematic insights into identification of biomarkers for TACE treatment sensitivity in HCC.
代谢重编程在肝细胞癌（HCC）的治疗效果中起重要作用。然而，与HCC经动脉化疗栓塞（TACE）治疗敏感性相关的代谢重编程关键基因仍有待进一步研究。
我们分析了来自公共数据库（癌症基因组图谱和基因表达综合数据库）的数据以及代谢相关基因（MRGs），以确定与TACE治疗敏感性相关的关键基因。对关键基因与免疫细胞浸润、HCC相关基因、调控网络构建、列线图构建及药物敏感性分析之间的关系进行了进一步分析。最后，基于数据库和体外逆转录定量聚合酶链反应（RT-qPCR）验证关键基因的表达。
鉴定出四个与TACE治疗敏感性相关的关键基因（细胞分裂周期蛋白20（CDC20）、溶血磷脂酰胆碱酰基转移酶1（LPCAT1）、对氧磷酶1（PON1）和分泌型磷酸蛋白1（SPP1））。与正常组织相比，肿瘤组织中以及晚期患者与早期患者相比，CDC20、LPCAT1和SPP1表达增加，PON1表达降低。与无反应患者相比，反应性患者中CDC20、LPCAT1和SPP1表达较低，PON1表达较高。CDC20、LPCAT1和SPP1高表达且PON1低表达的患者预后较差。它们还与肿瘤免疫微环境和对多种化疗药物的敏感性相关。在基因和蛋白水平验证了关键基因的表达。
我们的研究为鉴定HCC中TACE治疗敏感性的生物标志物提供了系统的见解。
