Bioinformatics analysis of the Hub genes and key pathways of interstitial cystitis pathogenesis

Abstract

Aims: This study aimed to identify suitable datasets for reanalysis and then explore potential key genes and related pathways of interstitial cystitis (IC). Methods:We searched the Gene Expression Omnibus database and three expression profile datasets and included 23 lesions of IC and 9 normal tissues in the analysis. Eight urine specimens of patients with IC and five urine specimens of healthy controls were also included. Then, these datasets were reanalyzed to determine the differentially expressed genes (DEGs), which were used to perform Gene Ontology and pathway enrichment analyses. These identified candidate genes were also applied to generate a protein-protein interaction (PPI) network.Results: Forty-two common DEGs were sorted and identified from two datasets, both of which included the samples of bladder lesions. Based on their functions and signaling pathways, these 42 DEGs are mainly classified as cell-surface proteins and are involved in the immune and inflammatory responses. The PPI network included 41 nodes. In this network, we identified 11 genes as central nodes that are involved in the immune system and the inflammatory response. Furthermore, IC with Hunner's lesions shared the same DEGs with IC without Hunner's lesions. In both subgroups (IC with and without Hunner's lesions), we identified some common DEGs shared between bladder lesions and urine samples. Conclusion: Using bioinformatics, we integrated different IC-related datasets and identified potential critical genes involved in IC that may contribute to future research on IC. K E Y W O R D Sbioinformatic, differentially expressed genes, interstitial cystitis

Identification of key genes in human urothelial cells corresponding to interstitial cystitis/bladder pain syndrome in a lipopolysaccharide‐induced cystitis model

“…One previous study 9 identified PNOC, SSTR1, and FPR3 as key genes in ulcerative IC/BPS, the results in which were not consistent with that in the research by Saha et al 10 However in the study by Liu et al, 11 authors found that 11 genes related to the immune system and the inflammatory response were key genes, including NCF2, S100A8, AQP9, S100A12, ITGAX, PROK2, PPBP, FPR1, CSF3R, LILRB3, and FCN1. Gene analysis regarding full‐thickness bladder tissue masked the important molecular mechanism of epithelial cells in IC/BPS.…”

“…Importantly, denudation or anatomical loss of urothelium is common in IC/BPS 8 . Considering that the molecular mechanism of IC/BPS is unclear, several studies have investigated the key genes and significant signaling pathways that drive IC/BPS 9–11 . However, the researchers sequenced the genes from the full‐thickness bladder tissues and the acquired findings were not consistent 9–11 .…”

“…Considering that the molecular mechanism of IC/BPS is unclear, several studies have investigated the key genes and significant signaling pathways that drive IC/BPS 9–11 . However, the researchers sequenced the genes from the full‐thickness bladder tissues and the acquired findings were not consistent 9–11 . Obviously, these results cannot reflect the transcriptome at the single‐cell level, but only the overall average RNA expression.…”

Biomarkers in the Light of the Etiopathology of IC/BPS

“…Besides alterations in single genes, specific alterations in protein networks and signaling pathways have also been identified in IC/BPS patients by bioinformatic analysis of public expression data sets in the GEO database [ 24 ]. Despite the number of available expression data sets in IC/BPS was still very small (23 IC lesions vs. 9 normal tissues), the authors found 42 differentially expressed genes (DEGs).…”

Interstitielle Zystitis: Was gibt es Neues zur Ätiopathogenese?

“…Neben Veränderungen einzelner Gene wurden auch spezifische Veränderungen in den Netzwerken/Signalwegen von IC/BPS-Patienten gefunden [15]. Mittels Genexpressionsanalyse aus urothelialem Biopsiematerial ließen sich 42 Differentiell Exprimierte Gene (DEGs) aus dem Material von IC/BPS-Patienten bestimmen, in denen 11 zentrale Knotengene identifiziert werden konnten.…”