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Background <p>Laryngeal squamous cell carcinoma (LSCC) is a heterogeneous malignancy, and conventional staging and grading remain insufficient for precise prognostic stratification. RNA methylation is involved in tumor progression, but its biological and prognostic significance in LSCC remains unclear.</p> Methods <p>We integrated transcriptomic and clinical data from 164 patients with LSCC and 12 normal tissue samples to analyse 35 RNA methylation-associated genes. Molecular subtypes and a prognostic signature were identified using consensus clustering, least absolute shrinkage and selection operator (LASSO), and Cox regression. Model performance was evaluated by receiver operating characteristic (ROC) curves and a nomogram. SHAP, immune infiltration, and drug sensitivity analyses were subsequently performed. EPYC was validated by in vitro assays, xenograft experiments, and preliminary METTL3-related m6A analyses.</p> Results <p>Twenty-eight genes were differentially expressed in LSCC, with frequent CNV gains and a mutation rate of 33.33%. Two RNA methylation-related subtypes with distinct prognoses and biological features were identified. A 4-gene signature (TFF2, S1PR4, STC2, and EPYC) showed moderate predictive value for overall survival. EPYC was upregulated in LSCC and associated with poor prognosis. EPYC knockdown suppressed proliferation, migration, invasion, and epithelial–mesenchymal transition in vitro and tumor growth in vivo. MeRIP–qPCR and METTL3 knockdown provided preliminary evidence that EPYC transcripts may undergo METTL3-related m6A modification. High-risk patients also showed distinct immune infiltration and predicted drug sensitivity profiles.</p> Conclusions <p>RNA methylation-associated genes define clinically relevant subtypes and a 4-gene prognostic signature in LSCC. EPYC is a biologically relevant risk-associated gene, with preliminary evidence of METTL3-related m6A regulation.</p>

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Integrated analysis of RNA methylation-associated signatures identifies a four-gene prognostic signature and EPYC as a risk-associated gene in LSCC

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年5月22日

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  • Yuehao Lu,
  • Ge Gao,
  • Nanxiang Chen,
  • Duanshali Liu,
  • Qin Che,
  • Haiming Xu,
  • Yilun Zou,
  • Bilan Xiong,
  • Gege Li,
  • Kai Zhao,
  • Mingbo Liu

摘要

Background

Laryngeal squamous cell carcinoma (LSCC) is a heterogeneous malignancy, and conventional staging and grading remain insufficient for precise prognostic stratification. RNA methylation is involved in tumor progression, but its biological and prognostic significance in LSCC remains unclear.

Methods

We integrated transcriptomic and clinical data from 164 patients with LSCC and 12 normal tissue samples to analyse 35 RNA methylation-associated genes. Molecular subtypes and a prognostic signature were identified using consensus clustering, least absolute shrinkage and selection operator (LASSO), and Cox regression. Model performance was evaluated by receiver operating characteristic (ROC) curves and a nomogram. SHAP, immune infiltration, and drug sensitivity analyses were subsequently performed. EPYC was validated by in vitro assays, xenograft experiments, and preliminary METTL3-related m6A analyses.

Results

Twenty-eight genes were differentially expressed in LSCC, with frequent CNV gains and a mutation rate of 33.33%. Two RNA methylation-related subtypes with distinct prognoses and biological features were identified. A 4-gene signature (TFF2, S1PR4, STC2, and EPYC) showed moderate predictive value for overall survival. EPYC was upregulated in LSCC and associated with poor prognosis. EPYC knockdown suppressed proliferation, migration, invasion, and epithelial–mesenchymal transition in vitro and tumor growth in vivo. MeRIP–qPCR and METTL3 knockdown provided preliminary evidence that EPYC transcripts may undergo METTL3-related m6A modification. High-risk patients also showed distinct immune infiltration and predicted drug sensitivity profiles.

Conclusions

RNA methylation-associated genes define clinically relevant subtypes and a 4-gene prognostic signature in LSCC. EPYC is a biologically relevant risk-associated gene, with preliminary evidence of METTL3-related m6A regulation.