PDF(Pubmed)
Abstract：
Leprosy and psoriasis rarely coexist, the specific molecular mechanisms underlying their mutual exclusion have not been extensively investigated. This study aimed to reveal the underlying mechanism responsible for the mutual exclusion between psoriasis and leprosy. We obtained leprosy and psoriasis data from ArrayExpress and GEO database. Differential expression analysis was conducted separately on the leprosy and psoriasis using DEseq2. Differentially expressed genes (DEGs) with opposite expression patterns in psoriasis and leprosy were identified, which could potentially involve in their mutual exclusion. Enrichment analysis was performed on these candidate mutually exclusive genes, and a protein-protein interaction (PPI) network was constructed to identify hub genes. The expression of these hub genes was further validated in an external dataset to obtain the critical mutually exclusive genes. Additionally, immune cell infiltration in psoriasis and leprosy was analyzed using single-sample gene set enrichment analysis (ssGSEA), and the correlation between critical mutually exclusive genes and immune cells was also examined. Finally, the expression pattern of critical mutually exclusive genes was evaluated in a single-cell transcriptome dataset. We identified 1098 DEGs in the leprosy dataset and 3839 DEGs in the psoriasis dataset. 48 candidate mutually exclusive genes were identified by taking the intersection. Enrichment analysis revealed that these genes were involved in cholesterol metabolism pathways. Through PPI network analysis, we identified APOE, CYP27A1, FADS1, and SOAT1 as hub genes. APOE, CYP27A1, and SOAT1 were subsequently validated as critical mutually exclusive genes on both internal and external datasets. Analysis of immune cell infiltration indicated higher abundance of 16 immune cell types in psoriasis and leprosy compared to normal controls. The abundance of 6 immune cell types in psoriasis and leprosy positively correlated with the expression levels of APOE and CYP27A1. Single-cell data analysis demonstrated that critical mutually exclusive genes were predominantly expressed in Schwann cells and fibroblasts. This study identified APOE, CYP27A1, and SOAT1 as critical mutually exclusive genes. Cholesterol metabolism pathway illustrated the possible mechanism of the inverse association of psoriasis and leprosy. The findings of this study provide a basis for identifying mechanisms and therapeutic targets for psoriasis.
摘要：
麻风病和牛皮癣很少共存，它们相互排斥的具体分子机制尚未得到广泛研究.本研究旨在揭示银屑病与麻风病相互排斥的潜在机制。我们从ArrayExpress和GEO数据库获得了麻风病和银屑病数据。使用DEseq2分别对麻风病和银屑病进行差异表达分析。鉴定出在银屑病和麻风病中具有相反表达模式的差异表达基因(DEGs),这可能涉及他们的相互排斥。对这些相互排斥的候选基因进行了富集分析，并构建了蛋白质-蛋白质相互作用（PPI）网络来识别hub基因。在外部数据集中进一步验证了这些hub基因的表达，以获得关键的互斥基因。此外,免疫细胞浸润在银屑病和麻风病分析使用单样品基因组富集分析（ssGSEA），并且还检查了关键的互斥基因与免疫细胞之间的相关性。最后,在单细胞转录组数据集中评估了关键互斥基因的表达模式.我们在麻风病数据集中确定了1098个DEG，在银屑病数据集中确定了3839个DEG。通过取交叉点鉴定了48个候选互斥基因。富集分析显示这些基因参与胆固醇代谢途径。通过PPI网络分析，我们确认了APOE,CYP27A1、FADS1和SOAT1作为hub基因。APOE,CYP27A1和SOAT1随后在内部和外部数据集上被验证为关键的互斥基因。免疫细胞浸润分析表明，与正常对照组相比，银屑病和麻风病中16种免疫细胞类型的丰度更高。银屑病和麻风病中6种免疫细胞的丰度与APOE和CYP27A1的表达水平呈正相关。单细胞数据分析表明，关键的互斥基因主要在雪旺细胞和成纤维细胞中表达。这项研究确定了APOE，CYP27A1和SOAT1是关键的互斥基因。胆固醇代谢途径说明了银屑病与麻风病逆相关的可能机制。本研究结果为确定银屑病的发病机制和治疗靶点提供了依据。
