ArticleTranslational cancer research2025
Identifying senescent cells as prognostic biomarkers and therapeutic targets of nasopharyngeal carcinoma by integrated analysis of single-cell and bulk-RNA sequencing data.
Article in Translational cancer research, 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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Abstract
Background: Senescence is significantly associated with cancer promotion. This study aimed to characterize senescent cells at the single-cell level in nasopharyngeal carcinoma (NPC) and elucidate the phenotype of tumorigenic senescent cell clusters. Methods: The composition of NPC based on the single-cell sequencing dataset GSE150430 from clinical specimens of 15 treatment-naïve patients and one patient with chronic nasopharyngitis were investigated. Results: Using single-cell transcriptomics, we identified the major types of senescent cells in NPC and determined that senescent epithelial C3 cells and SPP1+ macrophages were associated with tumor progression, and expressed unique arrays of pro-tumor surface proteins and senescence-associated secretory phenotype (SASP) factors. SASP is endowed with inflammatory cytokines and chemokines, which involve in the process of 'inflammatory ageing' and tumor progression. Epithelial cell cluster C3 upregulated epithelial-mesenchymal transition (EMT)-related genes associated with tumor metastasis. SPP1+ macrophages displayed a distinct secretome dominated by pro-inflammatory cytokines such as CCL2, CCL8, and IL-6, and were more enriched in glycolytic pathways compared with other subpopulations of macrophages. In particular, the senescent cell population showed higher and stronger intercellular communication compared with the non-senescent cell population. Furthermore, C3 interacted with SPP1+ macrophages through ANGPTL4-SD2. Conclusions: Our findings reveal the important role of senescent cells in the development of NPC, highlighting potential therapeutic pathways and cancer prevention strategies.
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