| Summary: | The complexity of interstitial cystitis/bladder pain syndrome (IC/BPS) has led to considerable uncertainty in terms of diagnosis and prevalence of the condition. Here, we try to identify the IC/BPS-associated genes through an integrated analysis of Gene Expression Omnibus (GEO) datasets and confirm experimentally to predict the pathologic diagnosis of IC/BPS. Data mining analysis of GEO datasets (GSE621, GSE11783, GSE28242, and GSE57560) revealed a total of 53 (51 upregulated and two downregulated) common differentially expressed genes (DEGs) in IC/BPS. A protein–protein interaction (PPI) network was then constructed with the 53 common DEGs using Cytoscape v3.7.2, and subsequently, six hub genes (<i>CD5</i>, <i>CD38</i>, <i>ITGAL</i>, <i>IL7R</i>, <i>KLRB1</i>, and <i>IL7R</i>) were identified using cytoHubba v0.1 that were upregulated in IC/BPS. Enrichment analysis of common DEGs revealed that hematopoietic cell lineage, immune system, and T-cell receptor (TCR) signaling in naïve CD4+ T cell signaling pathways were prominently involved with the common 51 upregulated DEGs. The two common downregulated DEGs may enrich linoleic acid metabolism and synthesis of epoxy (EET) and dihydroxyeicosatrienoic acid (DHET) signaling pathways in IC/BPS. Moreover, our RT-PCR data confirmed that the expression of the five hub genes (<i>CD38</i>, <i>ITGAL</i>, <i>IL7R</i>, <i>KLRB1</i>, and <i>IL7R</i>) was significantly augmented in IC/BPS patients’ samples when compared with their normal counterparts. In this study, we systematically predict the significant biomarkers and possible signaling pathways involved in IC/BPS, confirming the differential expression of the hub genes in tissue samples from patients with IC/BPS. Thus, the hub genes might be used as potential diagnostic biomarkers of IC/BPS.
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