ArticleDiscover oncology2025
Prognostic and immune modulatory effects of ammonia-induced cell death in head and neck squamous cell carcinoma.
Article in Discover oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
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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.
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Who cites it
2 citing papers in PubMed.
- Ammonia in cancer: dual roles and therapeutic strategies.Cancer cell international · 2025Review
- Ammonia metabolism and ammonia-induced cell death: role in cancer therapy.Cell communication and signaling : CCS · 2025Review
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAmmonia metabolism plays a crucial role in cancer progression and immune modulation. However, the prognostic relevance and immunological effects of ammonia-induced cell death (ACD) in HNSC remain insufficiently studied. ACD is a newly characterized form of regulated cell death caused by pathological ammonia accumulation, leading to mitochondrial dysfunction, oxidative stress, and DNA damage.
methodsA prognostic model was developed using random survival forests (RSF), with performance evaluated through concordance index (C-index) and survival analysis. Immune landscape profiling was performed using ssGSEA and Tracking Tumor Immunophenotype (TIP) analysis. Single-cell transcriptomic data were also used to examine ACD-associated gene expression in distinct cellular populations.
resultsKM survival analysis revealed that a high ammonia-death signature (ADS) was significantly associated with worse survival outcomes. Multivariate Cox regression identified ADS as an independent predictor of prognosis. Immune profiling showed that high ADS correlated with an immunosuppressive microenvironment, reduced immune infiltration, and impaired immune function. Glutaminase (GLS) was identified as a key ACD-related gene with high diagnostic accuracy and prognostic relevance. Single-cell RNA sequencing analysis demonstrated elevated GLS expression in malignant and stromal cells, with cell-cell communication analysis suggesting its involvement in immune evasion and metabolic reprogramming.
conclusionsThis study establishes ADS as a novel prognostic biomarker in HNSC, linking ammonia metabolism with tumor progression and immune suppression. These findings highlight potential therapeutic targets for metabolic and immunotherapeutic interventions in HNSC.
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