Journal Article

Characteristic genes and immune landscape of interstitial cystitis

Zhou, Yan, Guo, Kuo, Chen, Wenbin, Hu, Jie, Feng, Jianyong, Yun, Yanrui, Li, Yongzhang, Han, Jianpeng, Wang, Junhao

2025

Overview

Interstitial cystitis (IC) was still a disease with the exclusive diagnosis and lacked an effective gold standard. It was of great significance to find diagnostic markers for IC. Our study was aimed to screen characteristic genes via machine learning algorithms, characterize the immune landscape of IC, and show correlations between characteristic genes and immune cell subtypes. RNA sequencing data sets on IC were downloaded from Gene Expression Omnibus (GEO) database, including GSE57560, GSE11783 and GSE621, whose corresponding platforms were GPL16699, GPL570 and GPL262 respectively. Three machine learning algorithms were applied for identification of characteristic gene for IC. Single sample Gene Set Enrichment Analysis (ssGSEA) was applied to figure out the immune cell infiltration (ICI) of IC and normal tissue samples. Correlation analysis was performed via Spearman test. Receiver operator characteristic curve (ROC) was used to evaluate diagnostic efficacy of key genes. CCL18, MMP10 and WIF1 were identified as characteristic gene via machine learning algorithms. MMP10 and CCL18 were with higher expression in IC tissues compared with normal bladder tissues, while WIF1 had lower expressionin IC tissues (P < 0.05). These three genes had good diagnostic efficacy for IC. Compared with normal bladder tissues, 18 immune cell subtypes were up-regulated in interstitial cystitis tissues (P < 0.05). MMP10 and CCL18 were positively correlated to immune scores in IC, while WIF1 was negatively correlated to immune scores (P > 0.05). We screened the feature genes, CCL18, MMP10 and WIF1, among the differentially expressed genes (DEGs) by three different machine learning algorithms. They showed good diagnostic performance in both training and testing cohorts and were potential diagnostic markers for IC. We paint the immune landscape of IC. In IC tissue, immune cell subtypes infiltrated extensively. Most immune cell subtypes were up-regulated in IC tissue, including mast cells, activated CD4 T cells, and regulatory T cells that suppress immune responses. MMP10 and CCL18 had positive correlation to ICI, while WIF was negatively correlated with ICI. MMP10 and CCL18 may be the driving factors of immune response or their expression levels may be increased by immune response. The effect of characteristic genes of IC on immune cell subtypes still needed to be further explored.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Adaptor Proteins, Signal Transducing - genetics / Algorithms / Biology and Life Sciences / Biomarkers / Bladder / CD4 antigen / Chemokines / Computer and Information Sciences / Correlation analysis / Cystitis / Cystitis, Interstitial - diagnosis / Cystitis, Interstitial - genetics / Cystitis, Interstitial - immunology / Datasets / Diagnosis / Disease / Effectiveness / Gene expression / Gene Expression Profiling / Gene sequencing / Gene set enrichment analysis / Genes / Genetic aspects / Humans / Immune response / Immune system / Immunoregulation / Inflammation / Interstitial cystitis / Learning algorithms / Leukocytes / Lymphocytes / Lymphocytes T / Machine Learning / Mast cells / Medicine and Health Sciences / Methods / Physical Sciences / Research and Analysis Methods / RNA sequencing / ROC Curve / Software / Stromelysin 2 / Support vector machines / Tissues / Urinary Bladder - immunology / Urinary Bladder - metabolism / Urinary Bladder - pathology