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Peer-reviewedCC BYDiscover Oncology

Ferroptosis-related lncRNA signature predicts prognosis and immune microenvironment remodeling in laryngeal squamous cell carcinoma

  1. 1Zhangzhou Affiliated Hospital of Fujian medical University

Abstract

Background Ferroptosis is an iron-dependent regulated cell death process increasingly recognized as a modulator of tumor progression and antitumor immunity. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in shaping the immune microenvironment of laryngeal squamous cell carcinoma (LSCC) remains unclear. Methods TCGA transcriptomic and clinical data were analyzed to identify ferroptosis-related lncRNAs (FRLs) through co-expression analysis. A prognostic signature was constructed using a predefined LASSO Cox-based modelling strategy followed by multivariate Cox regression. Survival performance was evaluated by Kaplan-Meier analysis, time-dependent ROC curves, calibration analysis, and the concordance index (C-index). Tumor immune infiltration was assessed using ssGSEA and ESTIMATE algorithms, and associations with immune checkpoint expression were examined. Results A four-lncRNA ferroptosis-related signature stratified LSCC patients into prognostically distinct groups and remained an independent predictor of overall survival in the TCGA-derived cohort. High-risk tumors exhibited reduced infiltration of activated CD8 + T cells, NK cells, and dendritic cells, along with enrichment of MDSCs. The risk score showed a weak-to-moderate negative correlation with PD-L1 expression and was associated with reduced adaptive immune signatures, suggesting an immune-cold phenotype that requires further experimental validation. Conclusions This study identifies a ferroptosis-related lncRNA signature associated with survival and immune microenvironment features in LSCC. These findings provide a hypothesis-generating framework for future experimental and clinical studies integrating ferroptosis-related biomarkers with immunotherapy research.

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BibTeX
@article{xu2026ferroptosisrelated,
  title = {{Ferroptosis-related lncRNA signature predicts prognosis and immune microenvironment remodeling in laryngeal squamous cell carcinoma}},
  author = {Haibo Xu and Meiling Xu and Huijie Weng and Zhiwei Zhao and Yibin Zhou and Guifen Cai},
  journal = {Discover Oncology},
  year = {2026},
  month = jul,
  doi = {10.1007/s12672-026-05647-0},
  url = {https://doi.org/10.1007/s12672-026-05647-0},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Ferroptosis-related lncRNA signature predicts prognosis and immune microenvironment remodeling in laryngeal squamous cell carcinoma
AU  - Haibo Xu
AU  - Meiling Xu
AU  - Huijie Weng
AU  - Zhiwei Zhao
AU  - Yibin Zhou
AU  - Guifen Cai
PY  - 2026
DA  - 2026/07/01
JO  - Discover Oncology
DO  - 10.1007/s12672-026-05647-0
UR  - https://doi.org/10.1007/s12672-026-05647-0
AB  - Background Ferroptosis is an iron-dependent regulated cell death process increasingly recognized as a modulator of tumor progression and antitumor immunity. However, the role of ferroptosis-related long non-coding RNAs (lncRNAs) in shaping the immune microenvironment of laryngeal squamous cell carcinoma (LSCC) remains unclear. Methods TCGA transcriptomic and clinical data were analyzed to identify ferroptosis-related lncRNAs (FRLs) through co-expression analysis. A prognostic signature was constructed using a predefined LASSO Cox-based modelling strategy followed by multivariate Cox regression. Survival performance was evaluated by Kaplan-Meier analysis, time-dependent ROC curves, calibration analysis, and the concordance index (C-index). Tumor immune infiltration was assessed using ssGSEA and ESTIMATE algorithms, and associations with immune checkpoint expression were examined. Results A four-lncRNA ferroptosis-related signature stratified LSCC patients into prognostically distinct groups and remained an independent predictor of overall survival in the TCGA-derived cohort. High-risk tumors exhibited reduced infiltration of activated CD8 + T cells, NK cells, and dendritic cells, along with enrichment of MDSCs. The risk score showed a weak-to-moderate negative correlation with PD-L1 expression and was associated with reduced adaptive immune signatures, suggesting an immune-cold phenotype that requires further experimental validation. Conclusions This study identifies a ferroptosis-related lncRNA signature associated with survival and immune microenvironment features in LSCC. These findings provide a hypothesis-generating framework for future experimental and clinical studies integrating ferroptosis-related biomarkers with immunotherapy research.
SN  - 2730-6011
ER  -