【摘要】 目的 探讨铜死亡相关基因（cuproptosis-related genes, CRGs）在急性肝衰竭（acute liver failure,ALF）中的表达、潜在作用机制及潜在生物标志物价值。方法 从GEO数据库中筛选ALF患者相关数据集并进行整合。通过R软件进行差异分析，筛选差异表达基因（differentially expressed genes, DEGs），并进行基因集富集分析（gene set enrichment analysis, GSEA）;DEGs再与CRGs取交集，获得铜死亡相关ALF差异基因（ALF-specific cuproptosis-related genes, ALFCRGs）。通过ROC曲线分析关键基因ALF-CRGs的潜在生物标志物价值。分别通过qPCR和免疫组化验证ALF小鼠和患者肝组织中ALF-CRGs的表达。结果 共获得3 396个差异表达基因，GSEA显示DEGs富集于线粒体能量代谢（三羧酸循环、丙酮酸氧化）及铜稳态通路。筛选出7个ALF-CRGs，即FDX1、MT1M、MT1H、CYP1A1、ATP7B、NLRP3、AOC1;ROC曲线分析结果显示，AUC值均> 0.85。qPCR和免疫组化结果显示，FDX1、MT1M等ALF-CRGs在ALF中显著下调（P<0.05）。结论 FDX1等CRGs可能通过调控线粒体功能与铜稳态参与ALF进展，且对ALF具有较高的潜在生物标志物价值，可为ALF的早期诊断及靶向治疗提供重要依据和研究方向。更多还原

【Abstract】 Objective To explore the expression pattern, potential mechanisms and potential biomarker value of cuproptosis-related genes(CRGs) in acute liver failure(ALF). Methods The datasets related to ALF patients were obtained and integrated from GEO database. Differentially expressed genes(DEGs) were identified by R software and gene set enrichment analysis(GSEA) was conducted. ALF-specific cuproptosis-related genes(ALF-CRGs) were screened by intersecting DEGs with CRGs. The potential biomarker value of ALF-CRGs was analyzed by the ROC curve. In addition, the gene and protein expression of ALF-CRGs in the liver tissues of ALF mice and patients were verified by qPCR and immunohistochemistry respectively. Results A total of 3 396 DEGs were obtained. GSEA showed that the DEGs were enriched in mitochondrial energy metabolism(TCA cycle, pyruvate oxidation) and copper homeostasis pathways. A total of 7 ALF-CRGs were screened out namely, FDX1, MT1M, MT1H, CYP1A1, ATP7B, NLRP3 and AOC1. The ROC curve showed that the AUC values were > 0.85 for all ALF-CRGs. qPCR and immunohistochemistry detection showed that ALF-CRGs such as FDX1 and MT1M were significantly downregulated in ALF(P < 0.05). Conclusions CRGs such as FDX1 may participate in the progress of ALF by regulating mitochondrial function and copper homeostasis, and have high potential biomarker value for ALF, which provides an important basis and research direction for early diagnosis and targeted therapy of ALF.更多还原