What does this research mean for the field?

Bladder cancer adjacent tissue harbors distinct homeostatic and CCL2-high activated-like fibroblast states, and while a myCAF-associated gene signature correlates with pathological stage, it does not independently predict overall survival. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To characterize cancer-associated fibroblast diversity and immune-regulatory interactions within the bladder cancer tumor microenvironment.

August 31, 2026Frontiers in Cell and Developmental BiologyOpen Access

Single-cell transcriptomics deciphers cancer-associated fibroblast heterogeneity and immune regulatory mechanisms in the bladder cancer tumor microenvironment

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To characterize cancer-associated fibroblast diversity and immune-regulatory interactions within the bladder cancer tumor microenvironment.
Analyzed single-cell transcriptomic data (GSE135337) across 9,253 cells from bladder tumor and adjacent tissue using clustering, diffusion pseudotime, and LIANA ligand–receptor analyses.
Validated a six-gene myCAF score using bulk transcriptomic data from TCGA-BLCA (n = 401 after filtering) and GSE31684 (n = 93).
Performed RT-qPCR in RT4 and T24 bladder cancer cell lines to assess expression of select myCAF- and iCAF-associated genes.
Identified two adjacent-tissue fibroblast populations: homeostatic fibroblasts (n = 1,197) and CCL2-high activated-like fibroblasts (n = 726; CCL2 log2FC = 0.806, FDR = 8.08 × 10⁻¹¹), positioned at a later pseudotime state (median DPT 0.813 vs. 0.672).
A six-gene myCAF signature correlated with pathological stage in TCGA-BLCA (P = 1.60 × 10⁻¹²) and unadjusted survival (HR = 1.21, 95% CI: 1.02–1.42, P = 0.025), but was non-significant after age and stage adjustment (HR = 1.03, P = 0.748) and in GSE31684 (P = 0.443).
RT-qPCR showed 4.33- to 16.56-fold elevated expression of ACTA2, POSTN, MMP11, FAP, IL6, and CXCL12 in invasive T24 cells compared with RT4 cells (all BH-adjusted q < 0.01).

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Implication

Transcriptomic analysis reveals distinct fibroblast states and stage-associated gene scores in bladder cancer, indicating complex microenvironment interactions.

Cite This Study

He et al. (2026) studied this question.

synapsesocial.com/papers/6a9541eaf20e493292a741e2 https://doi.org/10.3389/fcell.2026.1889050

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Implication

Transcriptomic analysis reveals distinct fibroblast states and stage-associated gene scores in bladder cancer, indicating complex microenvironment interactions.

Single-cell transcriptomics deciphers cancer-associated fibroblast heterogeneity and immune regulatory mechanisms in the bladder cancer tumor microenvironment

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Discussion

Implication

Cite This Study

Single-cell transcriptomics deciphers cancer-associated fibroblast heterogeneity and immune regulatory mechanisms in the bladder cancer tumor microenvironment

Key Points

Discussion

Implication

Cite This Study

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