Department of Dermatology, Clinical Medical Research Center of Dermatology and Venereology in Hebei Province, Construction Unit of the Sub-Center of the National Center for Clinical Medical Research On Skin and Immunological Diseases, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People's Republic of China.
Sci Rep. 2024 Oct 11;14(1):23848. doi: 10.1038/s41598-024-75069-x.
The epidermal infiltration of neutrophils is a hallmark of psoriasis (PSO) and its activation leads to the release of neutrophil extracellular traps (NETs). However, the molecular mechanism of NETs-related genes (NETRGs) has not been extensively studied in PSO. To define NETs-related-biomarkers for PSO. The GSE13355 and GSE78097 datasets, and NETRGs gene set were included in this study. The datasets used in this study were all microarray data. The weighted gene co-expression network analysis (WGCNA) and machine learning algorithms were used to mine key genes. Later on, single-gene gene set enrichment analysis (GSEA) and immune infiltration analysis were implemented. Finally, the expression of key genes was verified using quantitative real-time fluorescence PCR (qRT-PCR). A total of 3 key genes (S100A9, CLEC7A, and CXCR4) were derived, and they all had excellent diagnostic performance. The single-gene GSEA enrichment results indicated that the key genes were mainly enriched in the chemokine signaling pathway and humoral immune response in the high-expression group, while focal adhesion was enriched in the low-expression group. The correlation analysis indicated that all key genes were strongly negatively correlated with resting mast cells and TGF-β family member receptor, while they were strongly positively correlated with activated CD4 memory T cells and antigen processing and presentation. Lastly, the experimental results showed that the expression trends of key genes were consistent with public database. In this study, we successfully screened three potential PSO diagnostic genes (S100A9, CLEC7A and CXCR4) that were closely related to NETs, and these findings not only provided new molecular marker candidates for the precise diagnosis of PSO patients, but also revealed possible future therapeutic targets. However, further in-depth research and validation were necessary.
中性粒细胞的表皮浸润是银屑病(PSO)的一个标志,其激活导致中性粒细胞细胞外陷阱(NETs)的释放。然而,PSO 中 NETs 相关基因(NETRGs)的分子机制尚未得到广泛研究。为了定义 PSO 的 NETs 相关生物标志物。本研究纳入了 GSE13355 和 GSE78097 数据集以及 NETRGs 基因集。本研究中使用的数据集均为微阵列数据。使用加权基因共表达网络分析(WGCNA)和机器学习算法挖掘关键基因。之后,进行了单基因基因集富集分析(GSEA)和免疫浸润分析。最后,使用定量实时荧光 PCR(qRT-PCR)验证关键基因的表达。共得出 3 个关键基因(S100A9、CLEC7A 和 CXCR4),它们都具有出色的诊断性能。单基因 GSEA 富集结果表明,关键基因在高表达组中主要富集在趋化因子信号通路和体液免疫反应中,而在低表达组中则富集在粘着斑中。相关性分析表明,所有关键基因均与静止肥大细胞和 TGF-β 家族成员受体呈强烈负相关,而与激活的 CD4 记忆 T 细胞和抗原加工呈强烈正相关和呈递。最后,实验结果表明关键基因的表达趋势与公共数据库一致。在这项研究中,我们成功筛选出三个与 NETs 密切相关的潜在 PSO 诊断基因(S100A9、CLEC7A 和 CXCR4),这些发现不仅为 PSO 患者的精确诊断提供了新的分子标记候选物,而且还揭示了可能的未来治疗靶点。然而,还需要进一步的深入研究和验证。