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Background <p>Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive malignancy with poor prognosis and low five-year survival rates. Ferroptosis, an iron-dependent form of cell death, has emerged as a potential factor in cancer therapy. This study aimed to identify differentially expressed genes (DEGs) associated with HNSCC, ferroptosis, and radiotherapy, and to develop a diagnostic model to establish novel biomarkers, early diagnosis and individualized therapy.</p> Methods <p>We analyzed TCGA-HNSCC, GSE6631, and GSE107591 datasets to identify Ferroptosis- and Radiotherapy-Related Differentially Expressed Genes (F&amp;RRDEGs).Ferroptosis &amp; radiotherapy scores were calculated, followed by immune infiltration and immunotherapy analyses. A Cox prognostic model was evaluated using nomograms, calibration curves, and decision curve analysis. Real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were used for experimental validation.</p> Results <p>11&#xa0;F&amp;RRDEGs were identified classifying two subtypes related to HNSCC.Significant differences were found in immune cell infiltration and immunophenoscore in CTLA4 and PD1/PD-L1/PD-L2 + CTLA4 between high and low ferroptosis &amp; radiotherapy scores(F&amp;Rs) groups. The 1-year calibration curve of the prognostic risk model showed better and more accurate performance and performance for the five-year prediction. RT-qPCR identified significant differences in the genes <i>ALOX12</i>,<i> EMP1</i>,<i> PIM1</i>, and <i>CA9</i> between the control and HNSCC groups, with WB confirming radiotherapy-induced upregulation of VDAC1/TFRC (pro-ferroptosis) and downregulation of GPX4/SLC7A11/FTH1 (anti-ferroptosis) in irradiated HNSCC cells.</p> Conclusion <p><i>ALOX12</i>,<i> EMP1</i>,<i> PIM1</i>, and <i>CA9</i> exhibited promising potential as diagnostic biomarkers. This study applies immune infiltration analysis to HNSCC research, offering fresh perspectives on patient-specific treatment plans, and accelerating the creation of focused therapies.</p>

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Ferroptosis and radiotherapy-related genes in head and neck squamous cell carcinoma: diagnostic and prognostic significance

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月15日

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  • Liyuan Fan,
  • Liang Shi,
  • Zhongchao Wang,
  • Jinghan Wang,
  • Yandong Mu

摘要

Background

Head and Neck Squamous Cell Carcinoma (HNSCC) is an aggressive malignancy with poor prognosis and low five-year survival rates. Ferroptosis, an iron-dependent form of cell death, has emerged as a potential factor in cancer therapy. This study aimed to identify differentially expressed genes (DEGs) associated with HNSCC, ferroptosis, and radiotherapy, and to develop a diagnostic model to establish novel biomarkers, early diagnosis and individualized therapy.

Methods

We analyzed TCGA-HNSCC, GSE6631, and GSE107591 datasets to identify Ferroptosis- and Radiotherapy-Related Differentially Expressed Genes (F&RRDEGs).Ferroptosis & radiotherapy scores were calculated, followed by immune infiltration and immunotherapy analyses. A Cox prognostic model was evaluated using nomograms, calibration curves, and decision curve analysis. Real-time quantitative PCR (RT-qPCR) and Western blotting (WB) were used for experimental validation.

Results

11 F&RRDEGs were identified classifying two subtypes related to HNSCC.Significant differences were found in immune cell infiltration and immunophenoscore in CTLA4 and PD1/PD-L1/PD-L2 + CTLA4 between high and low ferroptosis & radiotherapy scores(F&Rs) groups. The 1-year calibration curve of the prognostic risk model showed better and more accurate performance and performance for the five-year prediction. RT-qPCR identified significant differences in the genes ALOX12, EMP1, PIM1, and CA9 between the control and HNSCC groups, with WB confirming radiotherapy-induced upregulation of VDAC1/TFRC (pro-ferroptosis) and downregulation of GPX4/SLC7A11/FTH1 (anti-ferroptosis) in irradiated HNSCC cells.

Conclusion

ALOX12, EMP1, PIM1, and CA9 exhibited promising potential as diagnostic biomarkers. This study applies immune infiltration analysis to HNSCC research, offering fresh perspectives on patient-specific treatment plans, and accelerating the creation of focused therapies.