Inflammation-associated immune-related genes as potential biomarkers for the diagnosis of interstitial cystitis

炎症相关免疫相关基因作为间质性膀胱炎诊断的潜在生物标志物

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Abstract

Interstitial cystitis (IC) is a chronic inflammatory condition of the bladder, characterized by symptoms such as urinary frequency, urgency, and pelvic pain. An increasing amount of evidence points out that persistent inflammation and immune dysregulation are core characteristics of IC. This research aimed to pinpoint immune - related hub genes and validate their inflammatory roles. We got gene expression data of IC and control groups from GEO. The Limma package was employed to identify differentially expressed genes (DEGs), and subsequently, immune infiltration analysis was done via ssGSEA and module identification was performed using WGCNA. Hub genes were attained by integrating DEGs and WGCNA modules via PPI network analysis. Diagnostic performance was appraised by ROC curves. We created transcriptional and post - transcriptional regulatory networks with miRNet and NetworkAnalyst. Lastly, an LPS - instigated bladder epithelial inflammation model was used to validate key gene function. We pinpointed 2,422 DEGs which mainly concentrate in T-cell activation and inflammatory pathways. Ten hub genes (KIF11, DLGAP5, CEP55, CDK1, CCNB2, ASPM, TOP2A, NUSAP1, NDC80, and MELK) were tightly associated with immune regulation. Among the elements, MELK showed the greatest diagnostic value. Silencing MELK notably decreased The expression and secretion of interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in LPS-induced bladder epithelial cells, validating its pro - inflammatory function. ROC analysis demonstrate strong diagnostic potential of MELK. This research identified hub genes relevant to immunity and inflammation in IC, with MELK as a key factor promoting inflammatory cytokine production. These findings deepen the comprehension of IC pathogenesis and put forward MELK as a hopeful biomarker and therapeutic target.

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