Evidence map›Paper›PMID 40527915›Full record

ArticleNature communications2025

Bladder cancer variants share aggressive features including a CA125+ cell state and targetable TM4SF1 expression.

Heiko Yang, Hanbing Song, Elizabeth Yip, Timothy Gilpatrick, Kevin Chang, Paul Allegakoen, Kevin L Lu, Keliana Hui, Julia H Pham, Corynn Kasap and 9 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.

0numbers the graph read from it
0cells of the map it votes in
9citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

9 citing papers in PubMed.

  1. Article
  2. Review
  3. Observational
  4. Article
  5. Article
  6. Article
  7. Article
  8. Article
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

19 authors.

Heiko Yang *Department of Urology, University of California San Francisco, San Francisco, CA, USA.
Hanbing Song *Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-2164-8813
Elizabeth YipDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Timothy GilpatrickDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Kevin ChangDepartment of Urology, University of California San Francisco, San Francisco, CA, USA.
Paul AllegakoenDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Kevin L LuDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-2677-9537
Keliana HuiDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Julia H PhamDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Corynn KasapDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Vipul KumarDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Janae GayleDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Bradley A StohrDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.
Chien-Kuang Cornelia DingDepartment of Pathology, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0001-9047-0222
Arun P WiitaDepartment of Laboratory Medicine, University of California San Francisco, San Francisco, USA.ORCID http://orcid.org/0000-0002-7465-6964
Maxwell V MengDepartment of Urology, University of California San Francisco, San Francisco, CA, USA.
Jonathan ChouDivision of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, USA.ORCID http://orcid.org/0000-0003-1258-0391
Sima P PortenDepartment of Urology, University of California San Francisco, San Francisco, CA, USA.
Franklin W HuangDepartment of Urology, University of California San Francisco, San Francisco, CA, USA. franklin.huang@ucsf.edu.ORCID http://orcid.org/0000-0001-5447-0436

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Histologic variant (HV) subtypes of bladder cancer are clinically aggressive tumors that are more resistant to standard therapy compared to conventional urothelial carcinoma (UC). Little is known about the transcriptional programs that account for their biological differences. Here we show using single cell analysis that HVs harbor a tumor cell state characterized by expression of MUC16 (CA125), MUC4, and KRT24. This cell state is enriched in metastases, predicted to be highly resistant to chemotherapy, and linked with poor survival. We also find enriched expression of TM4SF1, a transmembrane protein, in HV tumor cells. Chimeric antigen receptor (CAR) T cells engineered against TM4SF1 protein demonstrated in vitro and in vivo activity against bladder cancer cell lines in a TM4SF1 expression-dependent manner, highlighting its potential as a therapeutic target.

Indexed as

CA-125 AntigenMembrane ProteinsNeoplasm ProteinsUrinary Bladder NeoplasmsAnimalsAntigens, SurfaceCell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansMiceMucin-4Single-Cell AnalysisXenograft Model Antitumor AssaysAntigens, SurfaceCA-125 AntigenMembrane ProteinsMUC16 protein, humanMucin-4Neoplasm ProteinsTM4SF1 protein, human

Identifiers

PMID40527915
PMCPMC12174346

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Registered trials

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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 OpenQuestion graph.