Liu Shengzhuo, Feng Shijian, Luo Deyi
Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Int Urogynecol J. 2019 Sep;30(9):1487-1495. doi: 10.1007/s00192-018-3817-x. Epub 2018 Nov 19.
This aim of this study was to better understand ulcerative interstitial cystitis/painful bladder syndrome (IC/PBS) at the molecular level and provide new clues related to diagnosis and treatment.
The microarray data set GSE11783, including the mRNA and miRNA profiles of bladder tissue obtained at cystoscopic biopsy from patients with ulcerative IC/PBS (presence of at least one Hunner's ulcer) and normal controls, was downloaded from the GEO (Gene Expression Omnibus) database (National Center for Biotechnology Information). These were evaluated using Greenspring GX and Ingenuity Pathway Analysis (IPA) software. The differentially expressed genes (DEGs) and miRNAs (DEMs) in these two groups were identified. Subsequently, the DEGs were subjected to functional analysis, and a protein-protein interaction (PPI) network was constructed. Finally, the miRNA-mRNA regulatory network was visualized using Cystoscope software.
Four DEMs and 1521 DEGs were identified between the ulcerative IC/PBS and control groups. The PPI network of the DEGs was constructed by STRING, which was composed of 393 nodes and 1039 edges, including 221 upregulated genes and 172 downregulated genes. Moreover, 27 genes in the PPI network were identified as hub genes in the IC/PBS group, e.g., PNOC, SSTR1, FPR3, GPR18 and APLNR. Subsequently, 27 clusters were selected from the PPI network using MCODE. It was shown that the most significant cluster consisted of 22 nodes and 231 edges. Moreover, miR-21 was the most significantly upregulated miRNA and was predicted to target one upregulated gene (RASGRP1) and two downregulated genes (KLF5 and SC5D).
The results of this data mining and integration provide further information on the possible molecular basis of IC/PBS pathogenesis as well as potential biomarkers and therapeutic targets for ulcerative IC/PBS diagnosis and treatment.
本研究旨在从分子水平更好地理解溃疡性间质性膀胱炎/疼痛性膀胱综合征（IC/PBS），并为诊断和治疗提供新线索。
从美国国立生物技术信息中心的基因表达综合数据库（GEO）下载微阵列数据集GSE11783，其中包括溃疡性IC/PBS患者（至少有一个Hunner溃疡）和正常对照在膀胱镜活检时获得的膀胱组织的mRNA和miRNA谱。使用Greenspring GX和 Ingenuity通路分析（IPA）软件对这些数据进行评估。鉴定这两组中差异表达的基因（DEGs）和miRNA（DEMs）。随后，对DEGs进行功能分析，并构建蛋白质-蛋白质相互作用（PPI）网络。最后，使用Cystoscope软件可视化miRNA-mRNA调控网络。
在溃疡性IC/PBS组和对照组之间鉴定出4个DEM和1521个DEG。DEGs的PPI网络由STRING构建，由393个节点和1039条边组成，包括221个上调基因和172个下调基因。此外，PPI网络中的27个基因被鉴定为IC/PBS组中的枢纽基因，例如PNOC、SSTR1、FPR3、GPR18和APLNR。随后，使用MCODE从PPI网络中选择27个聚类。结果显示，最显著的聚类由22个节点和231条边组成。此外，miR-21是上调最显著的miRNA，预计靶向一个上调基因（RASGRP1）和两个下调基因（KLF5和SC5D）。
本数据挖掘与整合结果为IC/PBS发病机制的可能分子基础以及溃疡性IC/PBS诊断和治疗的潜在生物标志物和治疗靶点提供了进一步信息。
