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鉴定银屑病中 PANoptosis 相关的生物标志物和免疫浸润特征。

Identification of PANoptosis-related biomarkers and immune infiltration characteristics in psoriasis.

机构信息

Henan University of Chinese Medicine, Zhengzhou, P.R. China.

Department of Dermatology, Henan Province Hospital of Traditional Chinese Medicine, The Second Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, P.R. China.

出版信息

Medicine (Baltimore). 2023 Oct 20;102(42):e35627. doi: 10.1097/MD.0000000000035627.

Abstract

BACKGROUND

PANoptosis may play a vital role in psoriasis. We investigated the relationship between PANoptosis in psoriasis.

METHODS

Genes information was mainly obtained from GeneCards and the gene expression omnibus database. Genefunctions identification was based on gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses. Gene set enrichment analysis was used to identify enriched signaling pathways in psoriasis. We constructed PPI networks using the search tool for the retrieval of interacting genes database and Cytoscape and explored mRNA-miRNA, mRNA-TF, and mRNA-drug interaction networks. Receiver operating characteristic curves were performed to screen potential biomarkers among these hub genes. Immune cell infiltration was analyzed using the Pearson algorithm, and the correlation between immune-cell abundance and PANoptosis-related differentially expressed gene (PDGs) was investigated.

RESULTS

We identified 10 PDGs, which were mainly involved in pyroptosis, cytokine-mediated signaling pathways, Salmonella infection and NOD-like receptor signaling pathway. The activated pathways were mostly proinflammatory and immunoregulatory pathways between immune cells. BAK1, CASP4, IL18, and IRF1 were identified as hub genes in the mRNA-miRNA network, and BAK1, IRF1, and PYCARD were hub genes in the mRNA-TF network. CASP1 was found to be the most targeted gene by drugs or molecular compounds. We found PDGs were positively associated with proinflammatory immune cell infiltration and negatively associated with anti-inflammatory or regulatory immune cells.

CONCLUSION

We confirmed the role of PANoptosis in psoriasis for the first time and predicted hub genes and immune characteristics, which provides new ideas for further investigation of psoriasis on pathogenic mechanisms and therapeutic strategies.

摘要

背景

细胞普遍凋亡可能在银屑病中发挥重要作用。我们研究了银屑病中细胞普遍凋亡的关系。

方法

基因信息主要从基因卡片和基因表达综合数据库获得。基因功能鉴定基于基因本体论和京都基因与基因组百科全书分析。基因集富集分析用于识别银屑病中富集的信号通路。我们使用搜索工具检索相互作用基因数据库和 Cytoscape 构建 PPI 网络,并探索 mRNA-miRNA、mRNA-TF 和 mRNA-药物相互作用网络。使用接收者操作特征曲线从这些枢纽基因中筛选潜在的生物标志物。使用 Pearson 算法分析免疫细胞浸润,研究免疫细胞丰度与细胞普遍凋亡相关差异表达基因(PDGs)之间的相关性。

结果

我们鉴定了 10 个 PDGs,它们主要参与细胞焦亡、细胞因子介导的信号通路、沙门氏菌感染和 NOD 样受体信号通路。激活的通路在免疫细胞之间大多是促炎和免疫调节通路。BAK1、CASP4、IL18 和 IRF1 被鉴定为 mRNA-miRNA 网络中的枢纽基因,BAK1、IRF1 和 PYCARD 被鉴定为 mRNA-TF 网络中的枢纽基因。Caspase1 是被药物或分子化合物靶向最多的基因。我们发现 PDGs 与促炎免疫细胞浸润呈正相关,与抗炎或调节免疫细胞呈负相关。

结论

我们首次证实了细胞普遍凋亡在银屑病中的作用,并预测了枢纽基因和免疫特征,为进一步研究银屑病的发病机制和治疗策略提供了新的思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dcfd/10589561/8a50240b4723/medi-102-e35627-g001.jpg

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