Wu Huaye, Yang Lu, Yuan Jiakun, Zhang Ling, Tao Qin, Yin Litong, Yu Xia, Lin Yonghong
Department of Obstetrics and Gynecology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Front Med (Lausanne). 2024 Jul 25;11:1435135. doi: 10.3389/fmed.2024.1435135. eCollection 2024.
Pelvic organ prolapse (POP) is a disease in which pelvic floor support structures are dysfunctional due to disruption of the extracellular matrix (ECM). The vascular system is essential for maintaining ECM homeostasis. Therefore, this study explored the potential mechanism of blood vessel development-related genes (BVDRGs) in POP.
POP-related datasets and BVDRGs were included in this study. Differentially expressed genes (DEGs) between the POP and control groups were first identified in the GSE12852 and GSE208271 datasets, and DE-BVDRGs were identified by determining the intersection of these DEGs and BVDRGs. Subsequently, the feature genes were evaluated by machine learning. Feature genes with consistent expression trends in the GSE12852 and GSE208271 datasets were considered key genes. Afterward, the overall diagnostic efficacy of key genes in POP was evaluated through receiver operating characteristic (ROC) curve analysis. Based on the key genes, enrichment analysis, immune infiltration analysis and regulatory network construction were performed to elucidate the molecular mechanisms underlying the functions of the key genes in POP.
A total of 888 DEGs1 and 643 DEGs2 were identified in the GSE12852 and GSE208271 datasets, and 26 candidate genes and 4 DE-BVDRGs were identified. Furthermore, Hyaluronan synthase 2 (HAS2), Matrix metalloproteinase 19 (MMP19) and Plexin Domain Containing 1 (PLXDC1) were identified as key genes in POP and had promising value for diagnosing POP (AUC > 0.8). Additional research revealed that the key genes were predominantly implicated in immune cell activation, chemotaxis, and cytokine release via the chemokine signaling pathway, the Nod-like receptor signaling pathway, and the Toll-like receptor signaling pathway. Analysis of immune cell infiltration confirmed a decrease in the proportion of plasma cells in POP, and MMP19 expression showed a significant negative correlation with plasma cell numbers. In addition, regulatory network analysis revealed that MALAT1 (a lncRNA) targeted hsa-miR-503-5p, hsa-miR-23a-3p and hsa-miR-129-5p to simultaneously regulate three key genes.
We identified three key BVDRGs (HAS2, MMP19 and PLXDC1) related to the ECM in POP, providing markers for diagnostic studies and investigations of the molecular mechanism of POP.
盆腔器官脱垂（POP）是一种由于细胞外基质（ECM）破坏导致盆底支持结构功能障碍的疾病。血管系统对于维持ECM稳态至关重要。因此，本研究探讨了血管发育相关基因（BVDRGs）在POP中的潜在机制。
本研究纳入了与POP相关的数据集和BVDRGs。首先在GSE12852和GSE208271数据集中鉴定出POP组和对照组之间的差异表达基因（DEGs），并通过确定这些DEGs与BVDRGs的交集来鉴定差异表达的BVDRGs（DE-BVDRGs）。随后，通过机器学习评估特征基因。在GSE12852和GSE208271数据集中具有一致表达趋势的特征基因被视为关键基因。之后，通过受试者工作特征（ROC）曲线分析评估关键基因在POP中的整体诊断效能。基于关键基因，进行富集分析、免疫浸润分析和调控网络构建，以阐明关键基因在POP中发挥功能的分子机制。
在GSE12852和GSE208271数据集中分别鉴定出888个DEGs1和643个DEGs2，鉴定出26个候选基因和4个DE-BVDRGs。此外，透明质酸合酶2（HAS2）、基质金属蛋白酶19（MMP19）和含丛蛋白结构域1（PLXDC1）被鉴定为POP中的关键基因，对诊断POP具有良好价值（AUC>0.8）。进一步研究表明，关键基因主要通过趋化因子信号通路、NOD样受体信号通路和Toll样受体信号通路参与免疫细胞激活、趋化和细胞因子释放。免疫细胞浸润分析证实POP中浆细胞比例降低，且MMP19表达与浆细胞数量呈显著负相关。此外，调控网络分析显示，MALAT1（一种长链非编码RNA）靶向hsa-miR-503-5p、hsa-miR-23a-3p和hsa-miR-129-5p以同时调节三个关键基因。
我们鉴定出了与POP中ECM相关的三个关键BVDRGs（HAS2、MMP19和PLXDC1），为POP的诊断研究和分子机制研究提供了标志物。
