■牛皮癣是一种以独特的鳞屑斑块为特征的慢性皮肤病。然而,在急性期,银屑病病变表现出湿疹性变化,使它们与特应性皮炎难以区分,这对生物制剂的选择提出了挑战。本研究旨在鉴定银屑病皮损中潜在的诊断基因并探讨其临床意义。
■对来自GEO数据库的GSE182740数据集进行差异分析;使用机器学习算法(SVM-RFE和LASSO回归模型)筛选诊断标志物;CIBERSORTx用于确定正常皮肤病变中22种不同免疫细胞成分的动态变化,银屑病非皮损,和银屑病皮损,以及诊断基因在10个主要免疫细胞中的表达,实时定量聚合酶链反应(RT-qPCR)和免疫组织化学用于验证结果。
■我们在银屑病患者的皮肤病变和非病变中获得了580个差异表达基因(DEGs),813DEGs在非病变和病变之间的混合患者,特应性皮炎的皮肤病变和非病变的96DEGs,分别。然后通过Veen图鉴定了牛皮癣中的144个特定DEG。最终,UGGT1、CCNE1、MMP9和ARHGEF28被鉴定为来自这144个特异性DEGs的潜在诊断基因。所选诊断基因的值通过扩展样品的受试者工作特征(ROC)曲线进行验证。4个诊断基因的ROC曲线下面积(AUC)超过0.7。RT-qPCR结果显示,与正常人表皮相比,UGGT1、CCNE1和MMP9在银屑病患者中的表达显著升高,而ARHGEF28表达显著降低。值得注意的是,CIBERSORTx结果显示CCNE1在CD4+T细胞和中性粒细胞中高表达,ARHGEF28也在肥大细胞中表达。此外,CCNE1与IL-17/CXCL8/9/10和CCL20密切相关。免疫组织化学结果表明,银屑病表皮细胞中CCNE1的核表达相对于正常细胞增加。
■基于这四个基因在ROC曲线中的表现及其在银屑病患者免疫细胞中的表达,我们建议CCNE1具有更高的诊断价值。
UNASSIGNED: Psoriasis is a chronic skin disease characterized by unique scaling plaques. However, during the acute phase, psoriatic lesions exhibit eczematous changes, making them difficult to distinguish from atopic dermatitis, which poses challenges for the selection of biological agents. This study aimed to identify potential diagnostic genes in psoriatic lesions and investigate their clinical significance.
UNASSIGNED: GSE182740 datasets from the GEO database were analyzed for differential analysis; machine learning algorithms (SVM-RFE and LASSO regression models) are used to screen for diagnostic markers; CIBERSORTx is used to determine the dynamic changes of 22 different immune cell components in normal skin lesions, psoriatic non-lesional skin, and psoriatic lesional skin, as well as the expression of the diagnostic genes in 10 major immune cells, and real-time quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry are used to validate results.
UNASSIGNED: We obtained 580 differentially expressed genes (DEGs) in the skin lesion and non-lesion of psoriasis patients, 813 DEGs in mixed patients between non-lesions and lesions, and 96 DEGs in the skin lesion and non-lesion of atopic dermatitis, respectively. Then 144 specific DEGs in psoriasis via a Veen diagram were identified. Ultimately, UGGT1, CCNE1, MMP9 and ARHGEF28 are identified for potential diagnostic genes from these 144 specific DEGs. The value of the selected diagnostic genes was verified by receiver operating characteristic (ROC) curves with expanded samples. The the area under the ROC curve (AUC) exceeded 0.7 for the four diagnosis genes. RT-qPCR results showed that compared to normal human epidermis, the expression of UGGT1, CCNE1, and MMP9 was significantly increased in patients with psoriasis, while ARHGEF28 expression was significantly decreased. Notably, the results of CIBERSORTx showed that CCNE1 was highly expressed in CD4+ T cells and neutrophils, ARHGEF28 was also expressed in mast cells. Additionally, CCNE1 was strongly correlated with IL-17/CXCL8/9/10 and CCL20. Immunohistochemical results showed increased nuclear expression of CCNE1 in psoriatic epidermal cells relative to normal.
UNASSIGNED: Based on the performance of the four genes in ROC curves and their expression in immune cells from patients with psoriasis, we suggest that CCNE1 possess higher diagnostic value.