Department of Clinical Laboratory, Chengdu Women's and Children's Central Hospital, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.
Department of Obstetrics and Gynecology, Chengdu Women's and Children's Central Hospital, School of Medicine, University of Electronic Science and Technology of China, No.1617 Ri Yue Street, Chengdu, 610091, Sichuan, China.
Int Urogynecol J. 2023 Jul;34(7):1395-1403. doi: 10.1007/s00192-022-05357-5. Epub 2022 Sep 22.
The pathogenesis of pelvic organ prolapse (POP) remains unknown. Herein, we aim to reveal the molecular profile of POP by transcriptomic and metabolomic analysis.
We selected 12 samples of uterosacral ligaments (USLs) from 6 POP patients and 6 controls for transcriptomic and metabolomic analyses. Differentially expressed genes (DEGs) were identified using the R package edgeR. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using clusterProfiler, and a protein-protein interaction (PPI) network was constructed using STRING and visualized in Cytoscape. Metabolomic profiling was performed by a liquid chromatography-tandem mass spectrometry system.
Transcriptomic analysis identified 487 DEGs between the POP and control groups. Functional enrichment analysis revealed that they were mostly related to immune response terms, including "adaptive immune response," "T cell differentiation," and "T cell activation." In addition, PTPRC, LCK, CD247, IL2RB, CD2, CXR5, JUN, CD3E, IL2RG, and PRF1 were the 10 nodes with the highest node degrees in the PPI network. Metabolomic profiling revealed 290 differentially expressed metabolites, which significantly enriched in "glycerophospholipid metabolism," "nicotinate and nicotinamide metabolism," "glycine, serine, and threonine metabolism," "arginine and proline metabolism," "pyrimidine metabolism," and "purine metabolism." Finally, integrated analysis revealed that the DEGs involved in these significantly enriched metabolic pathways included NT5C1A, GMPR, SDS, ALAS2, CARNS1, PYCR1, P4HA3, PGS1, and NMRK2.
Our findings demonstrate that the immune response and metabolic regulatory pathways are intertwined in POP and might provide new therapeutic targets.
盆腔器官脱垂（POP）的发病机制尚不清楚。在此，我们旨在通过转录组学和代谢组学分析揭示 POP 的分子特征。
我们选择了 6 名 POP 患者和 6 名对照者的 12 个子宫骶韧带（USL）样本进行转录组学和代谢组学分析。使用 R 包 edgeR 鉴定差异表达基因（DEGs）。使用 clusterProfiler 进行基因本体论（GO）和京都基因与基因组百科全书（KEGG）通路富集分析，并使用 STRING 构建蛋白质-蛋白质相互作用（PPI）网络，然后在 Cytoscape 中可视化。通过液相色谱-串联质谱系统进行代谢组学分析。
转录组分析在 POP 组和对照组之间鉴定出 487 个 DEGs。功能富集分析表明，它们主要与免疫反应相关，包括“适应性免疫反应”、“T 细胞分化”和“T 细胞激活”。此外，PPI 网络中节点度最高的 10 个节点为 PTPRC、LCK、CD247、IL2RB、CD2、CXR5、JUN、CD3E、IL2RG 和 PRF1。代谢组学分析揭示了 290 个差异表达的代谢物，这些代谢物显著富集于“甘油磷脂代谢”、“烟酸和烟酰胺代谢”、“甘氨酸、丝氨酸和苏氨酸代谢”、“精氨酸和脯氨酸代谢”、“嘧啶代谢”和“嘌呤代谢”。最后，综合分析表明，参与这些显著富集代谢途径的 DEGs 包括 NT5C1A、GMPR、SDS、ALAS2、CARNS1、PYCR1、P4HA3、PGS1 和 NMRK2。
我们的研究结果表明，免疫反应和代谢调节途径在 POP 中相互交织，可能为其提供新的治疗靶点。
