Evidence map›Paper›PMID 42874537›Full record

ArticleTranslational oncology2026

Single-cell and spatial transcriptomics reveal a DLL4-associated tip-like endothelial niche linked to neoadjuvant chemotherapy non-response in muscle-invasive bladder cancer.

Bochen Pan, Jiadong Zheng, Zuchao Luo, Shihao Hou, Caijun Yuan, Yang Wang, Xiangqian Cao, Letong Huang, Man Li, Haoyuan Wang and 1 more

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Article in Translational oncology, 2026. 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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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

11 authors.

Bochen PanDepartment of Urology, Clinical Medical College of Shanghai Tenth People's Hospital, Nanjing Medical University, Shanghai, China.
Jiadong ZhengDepartment of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Zuchao LuoKey Laboratory of Cancer Prevention and Treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China.
Shihao HouDepartment of Urology, Clinical Medical College of Shanghai Tenth People's Hospital, Nanjing Medical University, Shanghai, China.
Caijun YuanDepartment of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Yang WangDepartment of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Xiangqian CaoDepartment of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China.
Letong HuangKey Laboratory of Cancer Prevention and Treatment of Guizhou Province, Zunyi Medical University, Zunyi, 563000, China.
Man LiDepartment of Pathology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: 1805234@tongji.edu.cn.
Haoyuan WangDepartment of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: lcysehy@163.com.
Bing ShenDepartment of Urology, Clinical Medical College of Shanghai Tenth People's Hospital, Nanjing Medical University, Shanghai, China; Department of Urology, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China; Urologic Cancer Institute, School of Medicine, Tongji University, Shanghai, China; Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai, China. Electronic address: urodrshenbing@shsmu.edu.cn.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chemotherapy non-response remains a major challenge in bladder cancer, yet the endothelial states and intercellular communication programs associated with treatment failure remain poorly understood. Here, we integrated single-cell RNA sequencing, spatial transcriptomics, bulk transcriptomic data, computational analyses, and in vitro experiments to characterize endothelial programs associated with chemotherapy response. A non-response-related transcriptional program was preferentially enriched in endothelial cells and was most prominent in the TipEC_2 tip-like endothelial subset. Integrative analyses identified DLL4 as a key feature of this endothelial state. Spatial and ligand-receptor analyses further supported a DLL4-associated tip-like endothelial niche and inferred DLL4-NOTCH3-related communication between endothelial and malignant compartments, together with RBPJ-associated transcriptional activity in DLL4-positive TipEC_2 cells. Consistently, cisplatin-resistant bladder cancer cells showed increased expression of NOTCH3 and downstream transcriptional targets, whereas pharmacological Notch inhibition suppressed downstream HES1 and HEY1 expression and partially restored cisplatin sensitivity. Elevated DLL4 expression was associated with chemotherapy non-response and unfavorable survival. In a separate prognostic analysis, a DLL4-positive TipEC_2-associated risk model stratified patients by overall survival in TCGA-BLCA and GSE13507. Collectively, these findings identify a DLL4-associated tip-like endothelial niche linked to chemotherapy non-response and suggest DLL4-NOTCH3 signaling as a potential molecular link between vascular remodeling and treatment resistance in bladder cancer.

Indexed as

Bladder cancerChemoresistanceDLL4Single-cell rna sequencingSpatial transcriptomicsTumor endothelium

Identifiers

PMID42874537
PMCPMC13685988

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