Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis.
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...
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| Format: | Article |
| Language: | English |
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Public Library of Science (PLoS)
2024-01-01
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| Series: | PLoS ONE |
| Online Access: | https://doi.org/10.1371/journal.pone.0310362 |
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| author | Li Wu Xin-Long Jiao Ming Jing Sheng-Xiao Zhang Yang Wang Chen-Long Li Gao-Xiang Shi Zhuo-Yang Li Ge-Liang Liu Kai Yan Li-Xuan Yan Qi Wang Pei-Feng He Qi Yu |
| author_facet | Li Wu Xin-Long Jiao Ming Jing Sheng-Xiao Zhang Yang Wang Chen-Long Li Gao-Xiang Shi Zhuo-Yang Li Ge-Liang Liu Kai Yan Li-Xuan Yan Qi Wang Pei-Feng He Qi Yu |
| author_sort | Li Wu |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-d4dd97e9da534b39b1e705ccdbcde90b |
| institution | Kabale University |
| issn | 1932-6203 |
| language | English |
| publishDate | 2024-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj-art-d4dd97e9da534b39b1e705ccdbcde90b2024-11-09T05:31:54ZengPublic Library of Science (PLoS)PLoS ONE1932-62032024-01-011910e031036210.1371/journal.pone.0310362Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis.Li WuXin-Long JiaoMing JingSheng-Xiao ZhangYang WangChen-Long LiGao-Xiang ShiZhuo-Yang LiGe-Liang LiuKai YanLi-Xuan YanQi WangPei-Feng HeQi YuPsoriasis 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.https://doi.org/10.1371/journal.pone.0310362 |
| spellingShingle | Li Wu Xin-Long Jiao Ming Jing Sheng-Xiao Zhang Yang Wang Chen-Long Li Gao-Xiang Shi Zhuo-Yang Li Ge-Liang Liu Kai Yan Li-Xuan Yan Qi Wang Pei-Feng He Qi Yu Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis. PLoS ONE |
| title | Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis. |
| title_full | Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis. |
| title_fullStr | Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis. |
| title_full_unstemmed | Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis. |
| title_short | Discovery of PANoptosis-related signatures correlates with immune cell infiltration in psoriasis. |
| title_sort | discovery of panoptosis related signatures correlates with immune cell infiltration in psoriasis |
| url | https://doi.org/10.1371/journal.pone.0310362 |
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