Chen Zhen, Wang Xiaogang, Shao Yifan, Wang Kai, Xue Dong
Departments of Urology, The Third Affiliated Hospital of Soochow University, Changzhou, Jiangsu Province, China.
Department of Urology, Sir Run Run Hospital, Nanjing Medical University, Nanjing, Jiangsu Province, China.
Ann Med. 2025 Dec;57(1):2553930. doi: 10.1080/07853890.2025.2553930. Epub 2025 Sep 2.
Acute kidney injury (AKI) is a prevalent and life-threatening condition characterized by abrupt renal function decline and subsequent inflammatory cascades. PANoptosis has emerged as a significant contributor to the pathophysiology of AKI. This research aimed to explore the diagnostic and therapeutic implications of PANoptosis-related genes in AKI.
Kidney biopsy transcriptomic expression data were obtained from the GEO database. Differentially expressed genes (DEGs) associated with PANoptosis were identified between AKI and controls. WGCNA identified hub PANoptosis-related genes. PANoptosis scores and immune cell infiltration were calculated by ssGSEA. Machine learning algorithms was used to select feature genes. ROC analysis evaluated their diagnostic performance. Drug-gene interactions were explored.
We identified 3460 DEGs between AKI and controls (61 upregulated and 11 downregulated) related to PANoptosis, mainly enriched in cytokine signaling and apoptosis. Eight hub PANoptosis genes were identified. PANoptosis scores were significantly higher in AKI patients ( < 0.001). CASP8, CASP4, SFN, FAS, and CASP1 were selected as feature genes, with CASP8 having the highest AUC at 0.850 in the training set. A nomogram combining these genes demonstrated strong predictive power. Furthermore, these genes were related to immune cell infiltration positively and had potential drug associations. Validation in a renal ischemia-reperfusion injury rat model confirmed the upregulation of CASP8 ( < 0.01), CASP4 ( < 0.001), SFN ( < 0.0001), FAS ( < 0.01), and CASP1 ( < 0.01).
Our study identifies PANoptosis-related genes as potential diagnostic markers and therapeutic targets in AKI, highlighting their role in immune dysregulation in AKI.
急性肾损伤（AKI）是一种常见且危及生命的疾病，其特征为肾功能突然下降及随后的炎症级联反应。全程序死亡（PANoptosis）已成为急性肾损伤病理生理学的重要促成因素。本研究旨在探讨PANoptosis相关基因在急性肾损伤中的诊断和治疗意义。
从基因表达综合数据库（GEO数据库）获取肾活检转录组表达数据。在急性肾损伤组和对照组之间鉴定与PANoptosis相关的差异表达基因（DEG）。加权基因共表达网络分析（WGCNA）确定核心PANoptosis相关基因。通过单样本基因集富集分析（ssGSEA）计算PANoptosis评分和免疫细胞浸润情况。使用机器学习算法选择特征基因。ROC分析评估其诊断性能。探索药物-基因相互作用。
我们在急性肾损伤组和对照组之间鉴定出3460个与PANoptosis相关的差异表达基因（61个上调和11个下调），主要富集于细胞因子信号传导和凋亡。确定了8个核心PANoptosis基因。急性肾损伤患者的PANoptosis评分显著更高（<0.001）。半胱天冬酶8（CASP8）、半胱天冬酶4（CASP4）、原癌基因SFN（SFN）、凋亡因子（FAS）和半胱天冬酶1（CASP1）被选为特征基因，其中CASP8在训练集中的曲线下面积（AUC）最高，为0.850。结合这些基因的列线图显示出强大的预测能力。此外，这些基因与免疫细胞浸润呈正相关且具有潜在的药物关联。在肾缺血再灌注损伤大鼠模型中的验证证实了CASP8（<0.01）、CASP4（<0.001）、SFN（<0.0001）、FAS（<0.01）和CASP1（<0.01）的上调。
我们的研究确定PANoptosis相关基因是急性肾损伤潜在的诊断标志物和治疗靶点，突出了它们在急性肾损伤免疫失调中的作用。
