Single-cell spatial transcriptomics identifies SERPINE1 as a vascular endothelial mediator of cisplatin resistance in head and neck squamous cell carcinoma.
- 1Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China.
- 2Department of Rhinology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450052, China. Electronic address: [email protected].
Abstract
Background
Cisplatin resistance remains a major obstacle in head and neck squamous cell carcinoma (HNSCC), yet the contribution of the vascular microenvironment and its variation across HPV statuses remains unclear.Methods
We integrated single-cell RNA sequencing, spatial transcriptomics, and bioinformatics analyses to characterize cisplatin resistance-associated cellular states in HNSCC. Cisplatin resistance scoring, pseudotime analysis, transcriptional regulatory network analysis, and cell-cell communication analysis were used to identify resistant subpopulations. Spatial localization, survival analysis, immune infiltration assessment, and drug sensitivity prediction were further performed to evaluate key candidate genes.Results
Cisplatin resistance signals were preferentially enriched in tumor endothelial cells and were stronger in HPV-negative HNSCC. Endothelial cells with high resistance scores exhibited enhanced angiogenesis, extracellular matrix remodeling, hypoxia, and inflammatory programs. Multidimensional screening identified SERPINE1 as a key resistance-associated endothelial gene, showing significant upregulation and positive correlation with resistance scores. Single-cell and spatial transcriptomic analyses consistently demonstrated vascular-associated enrichment of SERPINE1, particularly in HPV-negative tumors. High SERPINE1 expression was associated with poor survival and an immunosuppressive tumor microenvironment. Drug sensitivity prediction suggested increased sensitivity of SERPINE1-high tumors to EGFR/SRC- and MAPK-pathway inhibitors, whereas no significant differences were observed for conventional cytotoxic agents.Conclusion
SERPINE1 defines a tumor endothelial state associated with cisplatin resistance in HNSCC and may contribute to HPV-related differences in the vascular microenvironment, providing a potential basis for therapeutic stratification.
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BibTeX
@article{su2026singlecell,
title = {{Single-cell spatial transcriptomics identifies SERPINE1 as a vascular endothelial mediator of cisplatin resistance in head and neck squamous cell carcinoma.}},
author = {Hongxia Su and Yuan Zhang and Jia Wang and Lei Liu and Yulin Zhao},
journal = {Translational oncology},
year = {2026},
month = oct,
doi = {10.1016/j.tranon.2026.103063},
url = {https://europepmc.org/article/MED/42868713},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - Single-cell spatial transcriptomics identifies SERPINE1 as a vascular endothelial mediator of cisplatin resistance in head and neck squamous cell carcinoma.
AU - Hongxia Su
AU - Yuan Zhang
AU - Jia Wang
AU - Lei Liu
AU - Yulin Zhao
PY - 2026
DA - 2026/10/13
JO - Translational oncology
DO - 10.1016/j.tranon.2026.103063
UR - https://europepmc.org/article/MED/42868713
AB - Background Cisplatin resistance remains a major obstacle in head and neck squamous cell carcinoma (HNSCC), yet the contribution of the vascular microenvironment and its variation across HPV statuses remains unclear.Methods We integrated single-cell RNA sequencing, spatial transcriptomics, and bioinformatics analyses to characterize cisplatin resistance-associated cellular states in HNSCC. Cisplatin resistance scoring, pseudotime analysis, transcriptional regulatory network analysis, and cell-cell communication analysis were used to identify resistant subpopulations. Spatial localization, survival analysis, immune infiltration assessment, and drug sensitivity prediction were further performed to evaluate key candidate genes.Results Cisplatin resistance signals were preferentially enriched in tumor endothelial cells and were stronger in HPV-negative HNSCC. Endothelial cells with high resistance scores exhibited enhanced angiogenesis, extracellular matrix remodeling, hypoxia, and inflammatory programs. Multidimensional screening identified SERPINE1 as a key resistance-associated endothelial gene, showing significant upregulation and positive correlation with resistance scores. Single-cell and spatial transcriptomic analyses consistently demonstrated vascular-associated enrichment of SERPINE1, particularly in HPV-negative tumors. High SERPINE1 expression was associated with poor survival and an immunosuppressive tumor microenvironment. Drug sensitivity prediction suggested increased sensitivity of SERPINE1-high tumors to EGFR/SRC- and MAPK-pathway inhibitors, whereas no significant differences were observed for conventional cytotoxic agents.Conclusion SERPINE1 defines a tumor endothelial state associated with cisplatin resistance in HNSCC and may contribute to HPV-related differences in the vascular microenvironment, providing a potential basis for therapeutic stratification.
SN - 1936-5233
ER -