Abstract

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 (CD5, CD38, ITGAL, IL7R, KLRB1, and IL7R) 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 (CD38, ITGAL, IL7R, KLRB1, and IL7R) 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.

Highlights

  • Interstitial cystitis/bladder pain syndrome (IC/BPS) is a prevalent condition that presents with symptoms of disrupted urine storage and pelvic pain

  • We revealed six hub genes, CD5, cluster of differentiation 38 (CD38), integrin alpha L chain (ITGAL), interleukin 7 receptor (IL7R), KRLB1, and proteasome subunit beta 9 (PSMB9), as novel biomarkers through bioinformatic analysis, and our experimental results with Korean patients confirmed that the hub genes could be potential diagnostic biomarkers for IC/BPS with Hunner lesions

  • The datasets samples included urine sediments and bladder tissues. These hub genes might be considered candidate biomarkers that can diagnose the disease in an invasive or non-invasive way. These hub genes may be regulated by various transcription factors, which may be related to IC/BPS

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Summary

Introduction

Interstitial cystitis/bladder pain syndrome (IC/BPS) is a prevalent condition that presents with symptoms of disrupted urine storage and pelvic pain. The syndrome lacks definitive diagnostic tests or markers and is defined by a collection of symptoms reported by patients, making diagnosis subjective and clinician dependent. While pain related to the bladder is the hallmark symptom of IC/BPS, there is no single definition of IC/BPS that can both identify all IC/BPS cases and distinguish these cases from similar conditions, such as OAB, endometriosis, and vulvodynia [5]. Under these circumstances, chronic inflammation has been reported to have arisen after surgery in IC/BPS patients, which is frequently misdiagnosed. We conducted an extensive bioinformatic analysis to identify genes and transcriptional factors to determine whether these biomarkers meet the clinical criteria to confirm the diagnosis of IC/BPS

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