Evidence map›Paper›PMID 41214597›Full record

ArticleBMC cancer2025

TGF-β signaling and tumor microenvironment dynamics in bladder cancer progression post-BCG therapy: a longitudinal single-nucleus RNA-seq study.

Seo-Young Lee, Yun-Hee Lee, Tae-Min Kim, U-Syn Ha

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Article in BMC cancer, 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

4 authors.

Seo-Young LeeDepartment of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Yun-Hee LeeDepartment of Urology, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
Tae-Min Kim *Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. tmkim@catholic.ac.kr.
U-Syn Ha *Cancer Research Institute, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. ushamd@catholic.ac.kr.

Funding

National Research Foundation of Korea 2018R1D1A1B07049542, 2019R1A5A2027588, and 2019M3E5D3073104
6 · The paper itself

Abstract

backgroundAlthough non-muscle-invasive bladder cancer (NMIBC) frequently recurs and progresses despite BCG therapy, cellular mechanisms behind this remain unclear. Understanding the dynamics within the tumor microenvironment (TME) and identifying pathways associated with BCG resistance are crucial for improving NMIBC treatment.

methodsTo elucidate transcriptional dynamics and key cellular interactions in the TME, we performed longitudinal single-nucleus RNA sequencing of 9 NMIBC cases with three pairs of treatment-naïve and disease progression samples. The resulting 58,037 nuclei were subject to cell type and subtyping annotations along with cell-cell interaction analyses.

resultsOur analysis revealed marked interpatient heterogeneity in malignant cells, accompanied by copy number alterations associated with disease progression. TGF-β signaling emerged as a key pathway, showing gradual enrichment from pre-treatment to post-progression samples. Within the tumor microenvironment, we identified distinct subtypes including LAMP3 + dendritic cells and iCAF fibroblasts that followed unique pseudotime trajectories linked to progression. Cell-cell interaction analysis further highlighted critical ligand-receptor pairs such as DSC2-DSG2 and ENG-BMPR2, which were associated with poor clinical outcomes. These interactions may represent hypothesis-generating candidates that warrant further validation.

conclusionsThis study highlights key cellular and molecular mechanisms underlying bladder cancer progression Post-BCG treatment. Through single-nucleus RNA sequencing, we identified critical TME subtypes, TGF-β signaling involvement, and crucial ligand-receptor interactions such as DSC2-DSG2 and ENG-BMPR2, which may serve as preliminary biomarkers requiring confirmation in larger independent cohorts. These findings offer valuable insights into enhancement of treatment strategies and patient outcomes.

Indexed as

BCG VaccineTransforming Growth Factor betaTumor MicroenvironmentUrinary Bladder NeoplasmsDisease ProgressionFemaleGene Expression Regulation, NeoplasticHumansLongitudinal StudiesMaleRNA-SeqSignal TransductionSingle-Cell AnalysisBCG VaccineTransforming Growth Factor betaBCGBladder cancerFibroblastMacrophageSingle-cell sequencingTGF- β signaling

Identifiers

PMID41214597
PMCPMC12599029

What Socratic holds

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LicenceCC BY
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.