DNA甲基化在银屑病和瘢痕疙瘩中的交叉机制研究

Research on the Cross Mechanism of DNA Methylation in Psoriasis and Keloids

摘要: 目的：瘢痕疙瘩(Keloid)是一种以成纤维细胞过度增殖和细胞外基质异常沉积为特征的良性真皮纤维增生性肿瘤，慢性炎症反应在瘢痕疙瘩的发生发展过程中发挥重要作用。银屑病作为一种典型的慢性炎症性皮肤疾病，在病理生理方面与瘢痕疙瘩存在部分重叠。本研究旨在通过生物信息学方法，识别可能介导两者发生发展的关键分子。方法：本研究采用差异表达分析和加权基因共表达网络分析(Weighted Gene Co-expression Network Analysis, WGCNA)探索交叉关键基因。寻找交叉关键基因的DNA甲基化位点并与银屑病和瘢痕疙瘩进行孟德尔随机化分析。结果：通过差异分析及WGCNA分析，筛选出银屑病与瘢痕疙瘩之间21个交叉关键基因，包括6个上调基因及15个下调基因。寻找交叉关键基因的DNA甲基化位点并进行孟德尔随机化分析，我们发现PLXND1的cg15504747位点与银屑病及瘢痕疙瘩之间同时存在显著的正相关性，对银屑病OR为1.08 (95% CI = 1.03~1.13, p = 0.0016)，对瘢痕疙瘩OR为1.20 (95% CI = 1.06~1.35, p = 0.0047)。结论：本研究筛选出与银屑病及瘢痕疙瘩相关的DNA甲基化位点，这可能有助于研究瘢痕疙瘩形成及发展的分子机制，同时可能成为未来药物治疗靶点之一。

Abstract: Objective: Keloid is a benign dermal fibroproliferative tumor characterized by excessive proliferation of fibroblasts and abnormal deposition of extracellular matrix. Chronic inflammatory response plays a significant role in the occurrence and development of keloids. Psoriasis, as a typical chronic inflammatory skin disease, shares some pathophysiological similarities with keloids. This study aims to identify key molecules that may mediate the occurrence and development of both conditions through bioinformatics methods. Methods: This study employed differential expression analysis and weighted gene co-expression network analysis (WGCNA) to explore cross-key genes. DNA methylation sites of the cross-key genes were identified and Mendelian randomization analysis was conducted for psoriasis and keloids. Results: Through differential analysis and WGCNA, 21 cross-key genes between psoriasis and keloids were screened out, including 6 up-regulated genes and 15 down-regulated genes. DNA methylation sites of the cross-key genes were identified and Mendelian randomization analysis was performed. We found that the cg15504747 site of PLXND1 was significantly positively correlated with both psoriasis and keloids, with an OR of 1.08 (95% CI = 1.03~1.13, p = 0.0016) for psoriasis and an OR of 1.20 (95% CI = 1.06~1.35, p = 0.0047) for keloids. Conclusion: This study identified DNA methylation sites related to psoriasis and keloids, which may help to understand the molecular mechanisms of keloid formation and development and may become a potential target for future drug treatment.