Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis

作者：Li Wu, Xin-long Jiao, Ming Jing, Sheng‐Xiao Zhang, Yang Wang, Chenlong Li, Gaoxiang Shi, Zhuoyang Li, Ge-liang Liu, Kai Yan, Li-xuan Yan, Qi Wang, P. F. He, Qi Yu · 发表于：PLoS ONE · 年份：2024 · DOI：10.1371/journal.pone.0310362 · 被引用次数：6 · 研究领域：Inflammasome and immune disorders、Psoriasis: Treatment and Pathogenesis、Immune cells in cancer

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 exhib...