鉴定 PLAC8 为间质性膀胱炎诊断的潜在生物标志物。

Identification of PLAC8 as a Potential Biomarker for the Diagnosis of Interstitial Cystitis.

机构信息

Department of Urology, The Affiliated Hospital of Qingdao Binhai University, Qingdao, 266404, China.

Department of Urology, Xiangyang Central Hospital, Affiliated Hospital of Hubei University of Arts and Science, Xiangyang, 441021, China.

出版信息

Comb Chem High Throughput Screen. 2024;27(13):1938-1947. doi: 10.2174/0113862073273817231107050852.

DOI:10.2174/0113862073273817231107050852

PMID:38441011

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.

CONCLUSION

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

间质性膀胱炎由于其病因和病理的复杂性，是一种病因不明的慢性疾病，需要排除其他疾病才能确诊。据我们所知，很少有研究针对间质性膀胱炎进行预测性生物标志物的鉴定。

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

从基因表达综合数据库（GEO）中检索间质性膀胱炎数据集。使用 R 包鉴定差异表达基因（DEGs），并进行功能和通路富集分析。通过 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验证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。使用 ssGSEA 鉴定与生物标志物密切相关的免疫细胞。通过免疫组织化学（IHC）检测患者中 PLAC8 的表达。

结果

鉴定出 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过程有关。PLAC8 作为间质性膀胱炎的生物标志物，在 IC 和正常膀胱组织之间的表达差异具有统计学意义。分析了与 PLAC8 相关的通路，重点关注 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，这与间质性膀胱炎的发病机制相似，间质性膀胱炎是一种慢性失调免疫性疾病。同时，我们也观察到 IC 组织中 PLAC8 的水平更高。