Decoding PANoptosis in Gout: Signature Gene Identification and Immune Infiltration Profiling

IF 2 4区医学 Q2 RHEUMATOLOGY

International Journal of Rheumatic Diseases Pub Date : 2025-07-04 DOI:10.1111/1756-185X.70344

Junjie Cao, Aifang Li, Gaiying Luo, Zhen Wu, Yuan Liu

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Abstract

Background

Gout is an inflammatory disorder triggered by the deposition of monosodium urate (MSU) crystals in joints and periarticular tissues. PANoptosis, a recently identified form of inflammatory cell death, remains uncharacterized in gout pathogenesis. This study aims to identify PANoptosis-related genes that may drive gout progression.

Methods

Gout-related datasets, including the human cohort (GSE160170) and murine model (GSE190138), were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were screened using thresholds of |log₂ fold change (FC)| ≥ 1 and adjusted P-value < 0.05. PANoptosis-related biomarkers were identified through the combined use of MCODE and cytoHubba algorithms in Cytoscape. Least Absolute Shrinkage and Selection Operator (LASSO) regression was applied to select hub genes. Subsequently, we performed single—sample gene set enrichment analysis (ssGSEA) for the hub genes, analyzed the infiltration levels of immune cells, constructed a miRNA–mRNA–transcription factor (TF) regulatory network, and identified potential therapeutic drugs via the DSigDB database and the Coremine Medical database. Finally, the expression of the diagnostic gene was validated by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR).

Results

The PANoptosis-associated gene SOCS3 was identified via integrative bioinformatics screening. Enrichment analysis and immune infiltration assessment revealed its involvement in gout pathogenesis through pathways linked to inflammation and cell death, with significant correlations observed with specific immune cell subsets. Clinical validation via RT-qPCR confirmed a strong consistency between SOCS3 expression levels in gout patients and computational predictions.

Conclusion

We identified the hub gene SOCS3 in gout and elucidated its mechanistic roles by integrated bioinformatics analysis, machine learning approach, and clinical validation, providing critical insights for advancing diagnostic biomarkers and therapeutic strategies in gout management.

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痛风PANoptosis的解码：特征基因鉴定和免疫浸润谱

痛风是一种炎症性疾病，由尿酸钠（MSU）晶体沉积在关节和关节周围组织引起。PANoptosis是最近发现的一种炎症细胞死亡形式，在痛风发病机制中仍未明确。本研究旨在确定panoptoosis相关基因可能驱动痛风的进展。方法从Gene Expression Omnibus （GEO）数据库中检索痛风相关数据集，包括人类队列（GSE160170）和小鼠模型（GSE190138）。筛选差异表达基因（DEGs）的阈值为|log2 fold change (FC)|≥1，调整p值<； 0.05。通过联合使用MCODE和cytoHubba算法在Cytoscape中鉴定panoptoosis相关的生物标志物。采用最小绝对收缩和选择算子（LASSO）回归筛选轮毂基因。随后，我们对枢纽基因进行了单样本基因集富集分析（ssGSEA），分析了免疫细胞的浸润水平，构建了mirna - mrna -转录因子（TF）调控网络，并通过DSigDB数据库和Coremine Medical数据库鉴定了潜在的治疗药物。最后，通过实时定量反转录聚合酶链反应（RT-qPCR）验证诊断基因的表达。结果通过综合生物信息学筛选，鉴定出panoptosis相关基因SOCS3。富集分析和免疫浸润评估显示其通过炎症和细胞死亡相关途径参与痛风发病，并与特异性免疫细胞亚群显著相关。通过RT-qPCR的临床验证证实了痛风患者中SOCS3表达水平与计算预测之间的高度一致性。结论通过综合生物信息学分析、机器学习方法和临床验证，我们确定了痛风的中枢基因SOCS3，并阐明了其机制作用，为推进痛风的诊断生物标志物和治疗策略提供了重要的见解。

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来源期刊

International Journal of Rheumatic Diseases RHEUMATOLOGY-

CiteScore

3.70

自引率

4.00%

发文量

362

审稿时长

1 months

期刊介绍： The International Journal of Rheumatic Diseases (formerly APLAR Journal of Rheumatology) is the official journal of the Asia Pacific League of Associations for Rheumatology. The Journal accepts original articles on clinical or experimental research pertinent to the rheumatic diseases, work on connective tissue diseases and other immune and allergic disorders. The acceptance criteria for all papers are the quality and originality of the research and its significance to our readership. Except where otherwise stated, manuscripts are peer reviewed by two anonymous reviewers and the Editor.