Feng Xiao, Yuan Xin, Hua Yang-Yang, Tao Jing, Zhang Nan
Department of Pathology, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital Zhengzhou Children's Hospital, Zhengzhou, 450018, China.
School of Biomedical Engineering, Tianjin Medical University, Tianjin, 322203, China.
Mol Biotechnol. 2025 May;67(5):2098-2110. doi: 10.1007/s12033-024-01186-7. Epub 2024 May 15.
Langerhans cell histiocytosis (LCH) is a rare condition predominantly affecting young children. Activation of the MAPK pathway has offered key new insights into the pathogenesis of LCH; however, the precise mechanisms underlying its occurrence and development are still far from being completely elucidated. There is still a relapse/reactivation rate in patients with multisystem LCH. Therefore, this study aimed to investigate other potential LCH pathophysiologies and prospective therapeutic targets. The gene expression omnibus (GEO) database was used to retrieve gene expression profiles of LCH (GSE16395). Three distinct types of analyses were performed after identifying the common differentially expressed genes (DEGs) in LCH: hub gene identification, functional annotation, module construction, drug repositioning, and expression analysis via immunohistochemistry (IHC). We identified 417 common DEGs and 50 central hub genes. This functional study highlighted the significance of keratinization, skin development, and inflammation. In addition, we predicted new drug candidates (RS2 drugs targeting matrix metalloprotease1, MMP1) that could be used for LCH treatment. Finally, gene-miRNA and gene-TF networks and immune cell infiltration were analyzed for MMP1-related genes. MMP1 expression levels in LCH tissues were validated by IHC. Our study identified the central communal genes and novel drug candidates. These shared pathways and hub genes offer new perspectives on future mechanisms of action and therapeutic targets.
朗格汉斯细胞组织细胞增多症（LCH）是一种主要影响幼儿的罕见疾病。丝裂原活化蛋白激酶（MAPK）信号通路的激活为LCH的发病机制提供了重要的新见解；然而，其发生和发展的精确机制仍远未完全阐明。多系统LCH患者仍存在复发/再激活率。因此，本研究旨在探究LCH其他潜在的病理生理学及前瞻性治疗靶点。利用基因表达综合数据库（GEO）检索LCH的基因表达谱（GSE16395）。在确定LCH中常见的差异表达基因（DEG）后，进行了三种不同类型的分析：核心基因鉴定、功能注释、模块构建、药物重新定位以及通过免疫组织化学（IHC）进行表达分析。我们鉴定出417个常见DEG和50个核心枢纽基因。这项功能研究突出了角质化、皮肤发育和炎症的重要性。此外，我们预测了可用于LCH治疗的新候选药物（靶向基质金属蛋白酶1即MMP1的RS2药物）。最后，分析了MMP1相关基因的基因- miRNA和基因-转录因子网络以及免疫细胞浸润情况。通过IHC验证了LCH组织中MMP1的表达水平。我们的研究鉴定出了核心共同基因和新的候选药物。这些共享通路和枢纽基因为未来的作用机制和治疗靶点提供了新的视角。
