Evidence map›Paper›PMID 41624768›Full record

ArticleFrontiers in molecular biosciences2025

A novel tumor-progressing fibroblast signature derived from single-cell RNA sequencing enables prognostic stratification and reveals RNF11 as a functional regulator in bladder cancer.

Miaoyu Zhang, Liangbin Lin, He Xu, Xu Su, Kui Zeng, Fangyang Zhong, Xianchao Su, Jie Chen, Min Cao, Hui Yu and 1 more

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In one paragraph

Article in Frontiers in molecular biosciences, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Miaoyu Zhang *Department of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Liangbin Lin *Medical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, China.
He Xu *Department of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Xu SuMedical Research Center, The Affiliated Hospital of Southwest Jiaotong University, The Third People's Hospital of Chengdu, Chengdu, China.
Kui ZengDepartment of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Fangyang ZhongDepartment of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Xianchao SuDepartment of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Jie ChenDepartment of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Min CaoDepartment of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Hui YuDepartment of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.
Hui ZhuoDepartment of Urology, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, College of Medicine, Southwest Jiaotong University, Chengdu, Sichuan, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background: Cancer-associated fibroblasts (CAFs) are key drivers of tumor progression in bladder cancer (BLCA), yet their molecular heterogeneity and prognostic utility remain incompletely characterized. Single-cell studies have revealed distinct CAF subpopulations with divergent clinical impacts, necessitating refined prognostic frameworks that capture CAF-mediated progression. Methods: We analyzed single-cell RNA sequencing data (GSE267718) from 8 BLCA patients to identify CAF populations and define progression-associated gene signatures. Using 359 TCGA-BLCA samples as the training cohort, we performed non-negative matrix factorization (NMF) consensus clustering on 85 prognostically significant CAF genes, identifying two molecular clusters with distinct survival outcomes. Through LASSO-Cox regression and stepwise selection, we constructed a four-gene Tumor-Progressing Fibroblast Riskscore model comprising Results: Single-cell analysis identified 557 differentially expressed genes between non-muscle-invasive bladder cancer and muscle-invasive bladder cancer CAFs. NMF clustering stratified TCGA patients into 2 clusters with significantly different overall survival. The TPFR model showed consistent prognostic performance in both training and validation cohorts, with high-risk patients showing significantly worse survival. Functional enrichment analysis revealed that TPFR scores correlated with ECM-receptor interaction, focal adhesion, and cytoskeletal regulation pathways. Stratified analysis revealed superior model performance in elderly (>60 years), male, and early-stage patients. In particular, Conclusion: We established a CAF-based prognostic model that integrates single-cell insights with bulk transcriptomics for robust risk stratification in BLCA. The TPFR model shows clinical utility particularly in elderly and early-stage patients. Functional characterization showed that RNF11 regulates proliferation and migration of bladder cancer. These findings highlight the prognostic value of CAF signatures and provide a framework for precision medicine approaches in bladder cancer management.

Indexed as

bladder cancercancer-associated fibroblastsprognostic modelRNF11single-cell RNA sequence

Identifiers

PMID41624768
PMCPMC12851964

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