Department of Anesthesiology, Shanxi Provincial People's Hospital, Taiyuan, China.
School of Basic Medical Sciences, Shanxi Medical University, Taiyuan, China.
PLoS One. 2024 Oct 31;19(10):e0310362. doi: 10.1371/journal.pone.0310362. eCollection 2024.
Psoriasis is an inflammatory skin disease that relapses frequently. Keratinocyte apoptosis dysregulation plays a crucial role in the pathological mechanisms of psoriasis. PANoptosis is a process with intermolecular interaction among pyroptosis, apoptosis, and necroptosis. The mechanism of PANoptosis in the occurrence and development of psoriasis is still unclear. Here we present a novel approach by identifying PANoptosis-related signatures (PANoptosis-sig) from skin tissue of psoriasis patients and healthy controls on transcriptional and protein levels. Five PANoptosis-sig (TYMP, S100A8, S100A9, NAMPT, LCN2) were identified. Enrichment analysis showed they were mainly enriched in response to leukocyte aggregation, leukocyte migration, chronic inflammatory response and IL-17 signaling pathway. Single cell transcriptome analysis showed TYMP and NAMPT were expressed in almost all cell populations, while LCN2, S100A8 and S100A9 were significantly highly expressed in keratinocyte. We then constructed predictive and diagnostic models with the PANoptosis-sig and evaluated their performance. Finally, unsupervised consensus clustering analysis was conducted to ascertain psoriasis molecular subtypes by the PANoptosis-sig. The psoriasis cohort was divided into two distinct subtypes. Immune landscape showed that the stromal score of cluster 1 was significantly higher than cluster 2, while the immune and estimate scores of cluster 2 were expressively higher than cluster 1. Cluster 1 exhibited high expression of Plasma cells, Tregs and Mast cells resting, while cluster 2 showed high expression of T cells, Macrophages M1, Dendritic cells activated, and Neutrophils in immune infiltration analysis. And cluster 2 was more sensitive to immune checkpoints. In conclusion, our findings revealed potential biomarkers and therapeutic targets for the prevention, diagnosis, and treatment of psoriasis, enhancing our understanding of the molecular mechanisms underlying PANoptosis.
银屑病是一种炎症性皮肤病，常反复发作。角质形成细胞凋亡失调在银屑病的病理机制中起着关键作用。PANoptosis 是一种焦亡、凋亡和坏死性凋亡之间存在分子间相互作用的过程。PANoptosis 在银屑病发生发展中的机制尚不清楚。在这里，我们通过在转录和蛋白水平上从银屑病患者和健康对照的皮肤组织中鉴定出 PANoptosis 相关特征（PANoptosis-sig），提出了一种新方法。鉴定出 5 个 PANoptosis-sig（TYMP、S100A8、S100A9、NAMPT、LCN2）。富集分析表明，它们主要富集在白细胞聚集、白细胞迁移、慢性炎症反应和 IL-17 信号通路的反应中。单细胞转录组分析表明，TYMP 和 NAMPT 在几乎所有细胞群中表达，而 LCN2、S100A8 和 S100A9 在角质形成细胞中表达明显上调。然后，我们使用 PANoptosis-sig 构建了预测和诊断模型，并评估了它们的性能。最后，通过 PANoptosis-sig 进行无监督共识聚类分析，确定银屑病的分子亚型。银屑病队列被分为两个不同的亚型。免疫图谱显示，簇 1 的基质评分明显高于簇 2，而簇 2 的免疫和估计评分明显高于簇 1。簇 1 中显示出浆细胞、Tregs 和静止肥大细胞的高表达，而簇 2 中显示出 T 细胞、M1 巨噬细胞、激活的树突状细胞和中性粒细胞的高表达。在免疫浸润分析中，簇 2 对免疫检查点更为敏感。总之，我们的研究结果揭示了潜在的生物标志物和治疗靶点，用于预防、诊断和治疗银屑病，增强了我们对 PANoptosis 分子机制的理解。
