Identification of Polyamine Metabolism-Related Biomarkers in Psoriasis: A Study Based on Transcriptomics and Single-Cell Sequencing

IF 3.4 3区 医学 Q1 DERMATOLOGY
Li Zhang, Xiaoqiang Jia, Xia Liu, Yanni Yang
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引用次数: 0

Abstract

Psoriasis (PS) is linked to altered polyamine metabolism, which may drive chronic inflammation and abnormal keratinocyte proliferation. We integrated transcriptomics and single-cell RNA sequencing (scRNA-seq) to identify polyamine metabolism-related genes (PMRGs) as biomarkers for PS and elucidate their mechanisms. Through the application of differential expression analysis, three machine learning algorithms, combined with receiver operating characteristic (ROC) analysis and expression quantification, biomarkers related to polyamine metabolism in PS were identified. Furthermore, the expression of these biomarkers was verified through western blotting. These biomarkers were subsequently incorporated into a diagnostic nomogram. Further investigations of these biomarkers included enrichment analysis and immune infiltration analysis. Additionally, scRNA-seq analysis was conducted to annotate the cell types in PS, providing insights into the cellular mechanisms underlying the progression of PS. In PS samples, biomarkers PSME2, PSMB5, PSMC4, PSMB10 and SMOX were significantly upregulated, achieving an area under the ROC curve (AUC) > 0.9 in GSE13355. Western blotting confirmed their upregulation, aligning with bioinformatics results. These biomarkers were closely associated with inflammation, cell proliferation, energy metabolism and signalling pathways. scRNA-seq identified 11 cell types, with mature dendritic cell (mDC) showing notable proportional differences between PS patients and controls, marking them as key cells. mDC exhibited distinct developmental trajectories with branching heterogeneity, featuring a reduction in early stages and an increase in later stages. Biomarker expression levels were higher in the later stages of mDC differentiation. The five PMRGs—PSME2, PSMB5, PSMC4, PSMB10 and SMOX—identified through comprehensive analyses, emerged as significant biomarkers for PS, providing promising diagnostic targets and mechanistic insights for the early detection and targeted treatment of PS.

银屑病多胺代谢相关生物标志物的鉴定:基于转录组学和单细胞测序的研究
银屑病(PS)与多胺代谢改变有关,这可能导致慢性炎症和异常角质细胞增殖。我们结合转录组学和单细胞RNA测序(scRNA-seq)技术鉴定了多胺代谢相关基因(PMRGs)作为PS的生物标志物,并阐明了其机制。通过应用差异表达分析、三种机器学习算法,结合受试者工作特征(ROC)分析和表达量化,鉴定出PS中与多胺代谢相关的生物标志物。此外,通过western blotting验证这些生物标志物的表达。这些生物标志物随后被纳入诊断图。这些生物标志物的进一步研究包括富集分析和免疫浸润分析。此外,scRNA-seq分析对PS中的细胞类型进行了注释,为PS进展的细胞机制提供了深入的了解。在PS样本中,生物标志物PSME2、PSMB5、PSMC4、PSMB10和SMOX显著上调,在GSE13355中实现了ROC曲线下面积(AUC) >.9。Western blotting证实了它们的上调,与生物信息学结果一致。这些生物标志物与炎症、细胞增殖、能量代谢和信号通路密切相关。scRNA-seq鉴定出11种细胞类型,其中成熟树突状细胞(mDC)在PS患者和对照组之间表现出显著的比例差异,标志着它们是关键细胞。mDC表现出明显的发育轨迹,具有分支异质性,表现为早期减少,后期增加。在mDC分化的后期,生物标志物的表达水平更高。通过综合分析鉴定出的5个PMRGs-PSME2、PSMB5、PSMC4、PSMB10和smox -成为重要的PS生物标志物,为PS的早期发现和靶向治疗提供了有希望的诊断靶点和机制见解。
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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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