关键词: Interstitial cystitis PLAC8 biomarker chemokine diagnosis. immune cells

Mesh : Humans Biomarkers / metabolism analysis Cystitis, Interstitial / diagnosis metabolism

来  源:   DOI:10.2174/0113862073273817231107050852

Abstract:
BACKGROUND: Interstitial cystitis is a diagnosis of exclusion due to the complexity of its etiology and pathology, which is a chronic disease with an unknown etiology. To our knowledge, few studies were performed to identify predictive biomarkers for interstitial cystitis.
OBJECTIVE: This study aimed to identify and validate potential biomarkers for Interstitial Cystitis (IC).
METHODS: The interstitial cystitis datasets were retrieved from the Gene Expression Omnibus (GEO) database. Differentially expressed genes (DEGs) were identified by using the R package and were subjected to functional and pathway enrichment analysis. Key biomarkers of interstitial cystitis were identified by using Lasso regression analysis and the SVM-RFE algorithm. The diagnostic value of key biomarkers was validated in internal and external datasets, and pathways that relate to biomarkers of interstitial cystitis were screened. The ssGSEA was employed to identify the immune cells closely related to biomarkers. The expression of PLAC8 in patients with interstitial cystitis was detected by Immune-Histochemistry (IHC).
RESULTS: Sixteen differentially expressed genes associated with interstitial cystitis were identified, which were primarily linked to the biological process of the chemokine signaling pathway. PLAC8, identified as a biomarker for interstitial cystitis, was validated to express a significantly different between IC and normal bladder tissues. PLAC8-related pathways were analyzed, with a focus on NF-κB, TNF, Toll-like receptor, chemokine, IL-17, and JAK-STAT signaling pathways. PLAC8 was proved to be closely related to immune activations, which is similar to the pathogenesis of IC, which is a chronic dysregulated immune disease. Meanwhile, we also observed a higher level of PLAC8 in IC tissues.
CONCLUSIONS: PLAC8 has promising application prospects as a biomarker for interstitial cystitis diagnosis. These findings could aid in the diagnosis and treatment of interstitial cystitis.
摘要:
背景:间质性膀胱炎是一种排除性诊断,由于其病因和病理的复杂性,这是一种病因不明的慢性疾病。据我们所知,很少有研究确定间质性膀胱炎的预测性生物标志物.
目的:本研究旨在鉴定和验证间质性膀胱炎(IC)的潜在生物标志物。
方法:从基因表达综合(GEO)数据库检索间质性膀胱炎数据集。通过使用R包鉴定差异表达基因(DEGs),并进行功能和途径富集分析。通过使用Lasso回归分析和SVM-RFE算法鉴定间质性膀胱炎的关键生物标志物。在内部和外部数据集中验证了关键生物标志物的诊断价值,并筛选与间质性膀胱炎生物标志物相关的通路。ssGSEA用于鉴定与生物标志物密切相关的免疫细胞。免疫组织化学(IHC)检测间质性膀胱炎患者PLAC8的表达。
结果:确定了16个与间质性膀胱炎相关的差异表达基因,主要与趋化因子信号通路的生物学过程有关。PLAC8被确定为间质性膀胱炎的生物标志物,证实在IC和正常膀胱组织之间表达显着差异。PLAC8相关通路进行了分析,专注于NF-κB,TNF,Toll样受体,趋化因子,IL-17和JAK-STAT信号通路。PLAC8被证明与免疫激活密切相关,这与IC的发病机制相似,这是一种慢性失调的免疫疾病。同时,我们还观察到IC组织中PLAC8水平较高。
结论:PLAC8作为间质性膀胱炎诊断的生物标志物具有良好的应用前景。这些发现有助于间质性膀胱炎的诊断和治疗。
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