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Background <p>Head and neck squamous cell carcinoma (HNSCC) represents a significant malignancy arising from mucosal epithelia. Pyroptosis, a gasdermin-mediated programmed necrotic cell death mechanism, has emerged as a critical process in tumor biology due to its association with inflammatory factor release and immune microenvironment modulation. While the interplay between inflammatory responses and tumorigenesis is well-established, the regulatory role of pyroptosis-related long non-coding RNAs (lncRNAs) in HNSCC progression remains poorly characterized. This investigation aims to elucidate the prognostic significance of pyroptosis-associated lncRNAs in HNSCC and their potential impact on tumor immunobiology.</p> Methods <p>Prognostic lncRNA signatures were subsequently established through univariate Cox regression followed by LASSO (Least Absolute Shrinkage and Selection Operator) and multivariate Cox proportional hazards modeling. The predictive capacity of the derived signature was validated through survival analysis, nomogram construction, and receiver operating characteristic (ROC) curve assessment. Immune microenvironment characteristics were investigated via Gene Set Enrichment Analysis (GSEA) and immune checkpoint expression profiling.</p> Results <p>Our analysis identified 18 differentially expressed pyroptosis-related lncRNAs with prognostic significance in HNSCC. Kaplan-Meier survival curves demonstrated superior overall survival in low-risk patients stratified by the lncRNA signature. The prognostic model achieved an area under the curve (AUC) of 0.663, outperforming conventional clinicopathological parameters. GSEA revealed significant enrichment of immune-related pathways in the low-risk cohort, including T-cell activation and cytokine-mediated signaling. Comprehensive immune profiling demonstrated differential activity in 34 immune checkpoints between risk groups, including CTLA4, PDCD1, and LAG3. Significant intergroup differences were observed in immunological parameters including HLA expression, T-cell cytolytic activity, and TNF-mediated signaling.</p> Conclusion <p>This study establishes a novel 18-lncRNA signature associated with pyroptosis and inflammatory responses in HNSCC, demonstrating robust prognostic capability and significant correlation with tumor immune landscape alterations. The identified biomarkers provide insights into pyroptosis-mediated immunomodulation and present potential targets for therapeutic intervention. Our findings underscore the clinical utility of pyroptosis-related lncRNA profiling in HNSCC risk stratification and immunotherapy response prediction.</p>

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The pyroptosis and inflammatory response-related long noncoding RNA signature as a novel prognostic biomarker of head and neck squamous cell carcinoma

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月19日

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  • Xian Xu,
  • Qian Liu,
  • Siyuan Liu,
  • Yide Zhang,
  • Mengqiao Yang,
  • Junkai Xue,
  • Peng Sun,
  • Jisheng Liu,
  • Ziang Gao

摘要

Background

Head and neck squamous cell carcinoma (HNSCC) represents a significant malignancy arising from mucosal epithelia. Pyroptosis, a gasdermin-mediated programmed necrotic cell death mechanism, has emerged as a critical process in tumor biology due to its association with inflammatory factor release and immune microenvironment modulation. While the interplay between inflammatory responses and tumorigenesis is well-established, the regulatory role of pyroptosis-related long non-coding RNAs (lncRNAs) in HNSCC progression remains poorly characterized. This investigation aims to elucidate the prognostic significance of pyroptosis-associated lncRNAs in HNSCC and their potential impact on tumor immunobiology.

Methods

Prognostic lncRNA signatures were subsequently established through univariate Cox regression followed by LASSO (Least Absolute Shrinkage and Selection Operator) and multivariate Cox proportional hazards modeling. The predictive capacity of the derived signature was validated through survival analysis, nomogram construction, and receiver operating characteristic (ROC) curve assessment. Immune microenvironment characteristics were investigated via Gene Set Enrichment Analysis (GSEA) and immune checkpoint expression profiling.

Results

Our analysis identified 18 differentially expressed pyroptosis-related lncRNAs with prognostic significance in HNSCC. Kaplan-Meier survival curves demonstrated superior overall survival in low-risk patients stratified by the lncRNA signature. The prognostic model achieved an area under the curve (AUC) of 0.663, outperforming conventional clinicopathological parameters. GSEA revealed significant enrichment of immune-related pathways in the low-risk cohort, including T-cell activation and cytokine-mediated signaling. Comprehensive immune profiling demonstrated differential activity in 34 immune checkpoints between risk groups, including CTLA4, PDCD1, and LAG3. Significant intergroup differences were observed in immunological parameters including HLA expression, T-cell cytolytic activity, and TNF-mediated signaling.

Conclusion

This study establishes a novel 18-lncRNA signature associated with pyroptosis and inflammatory responses in HNSCC, demonstrating robust prognostic capability and significant correlation with tumor immune landscape alterations. The identified biomarkers provide insights into pyroptosis-mediated immunomodulation and present potential targets for therapeutic intervention. Our findings underscore the clinical utility of pyroptosis-related lncRNA profiling in HNSCC risk stratification and immunotherapy response prediction.