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Updated: Aug 11, 2025
An Orthotopic Bladder Tumor Model and the Evaluation of Intravesical saRNA Treatment
Published on: July 28, 2012
Mapping the tumor microenvironment in bladder cancer and exploring the prognostic genes by single-cell RNA sequencing
Zhibin Chen1, Dongmao Chen1, Zhenfeng Song1
1Department of Urology and Andrology, Minimally Invasive Surgery Center, Guangdong Provincial KeyLaboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.
Abstract:
Despite substantial advances in the treatment using immune checkpoint inhibitors (ICIs), the clinical expected therapeutic effect on bladder cancer has not been achieved, in which the tumor microenvironment (TME) occupies a notable position. In this research, 10X single-cell RNA-sequencing technology was conducted to analyze seven primary bladder tumor tissues (three non-muscle-invasive bladder cancer (NMIBC) and four muscle-invasive bladder cancer (MIBC)) and seven corresponding normal tissues adjacent to cancer; eight various cell types were identified in the bladder cancer (BC) TME, and a complete TME atlas in bladder cancer was made. Moreover, bladder cancer epithelial cells were further subdivided into 14 subgroups, indicating a high intra-tumoral heterogeneity. Additionally, the differences between NMIBC and MIBC were compared based on differential gene expression heatmap, copy number variation (CNV) distribution heatmap, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Weighted gene co-expression network analysis (WGCNA), protein-protein interaction (PPI) network mutual analysis, and the Kaplan-Meier survival prognosis analysis were used to identify six key genes associated with the prognosis of bladder cancer: VEGFA, ANXA1, HSP90B1, PSMA7, PRDX6, and PPP1CB. The dynamic change of the expression distribution of six genes on the pseudo-time axis was further verified by cell pseudo-time analysis.
Insights
This study reveals the complex tumor microenvironment in bladder cancer using single-cell sequencing. Six key genes (VEGFA, ANXA1, HSP90B1, PSMA7, PRDX6, PPP1CB) were identified as crucial for bladder cancer prognosis.
Area of Science:
- Oncology
- Immunology
- Genomics
Background:
- Immune checkpoint inhibitors (ICIs) show limited efficacy in bladder cancer, partly due to the tumor microenvironment (TME).
- Understanding the bladder cancer TME is critical for improving therapeutic outcomes.
Purpose of the Study:
- To create a comprehensive atlas of the bladder cancer TME.
- To identify key genes associated with bladder cancer prognosis and intra-tumoral heterogeneity.
Main Methods:
- 10X single-cell RNA sequencing of bladder tumor and adjacent normal tissues.
- Bioinformatic analyses including differential gene expression, CNV analysis, GO, KEGG, WGCNA, PPI networks, and survival analysis.
- Cell pseudo-time analysis to track gene expression dynamics.
Main Results:
- Eight distinct cell types were identified in the bladder cancer TME, forming a detailed TME atlas.
- Bladder cancer epithelial cells exhibited significant intra-tumoral heterogeneity with 14 subgroups identified.
- Six key prognostic genes (VEGFA, ANXA1, HSP90B1, PSMA7, PRDX6, PPP1CB) were identified and their expression dynamics analyzed.
Conclusions:
- The study provides a detailed map of the bladder cancer TME and highlights significant intra-tumoral heterogeneity.
- The identified prognostic genes offer potential therapeutic targets for improving bladder cancer treatment outcomes.
