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Aim <p>To investigate the prognostic significance of histone acetylation (HAc) regulators in esophageal cancer (EC) and develop a transcriptome-based HAc_score reflecting epigenetic and immunogenomic states.</p> Methods <p>Expression and mutation from EC were analyzed to identify prognostic HAc regulators via univariable Cox models. Consensus clustering defined HAc-related expression patterns. Differentially expressed genes (DEGs) among clusters were functionally enriched. A principal component-based HAc_score was constructed from prognostic DEGs and tested for associations with overall survival, tumor mutational burden (TMB), immunophenoscore (IPS), and immune cell infiltration.</p> Results <p>Three HAc-related expression patterns showed distinct biological and immune features. From shared DEGs, 19 prognostic genes defined two molecular subtypes and served as the basis for the HAc_score. Higher HAc_score was associated with better overall survival, particularly in early-stage disease. HAc_score correlated inversely with TMB and positively with IPS components, suggesting a transcriptionally active, immunogenic phenotype despite lower mutation burden. Combining HAc_score with TMB improved risk stratification.</p> Conclusion <p>HAc_score quantifies HAc–linked transcriptional states in EC and reflects tumor–immune interactions. It stratifies survival risk and complements TMB, supporting its potential use as a prognostic biomarker and integrative epigenetic–immune signature.</p>

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A histone acetylation score for prognostic stratification and immunogenomic profiling in esophageal cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月29日

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  • Chanyuan Fan,
  • Kailun Sun,
  • Zhaoyan Feng,
  • Peipei Zhang,
  • Xi Yang,
  • Xiangde Min

摘要

Aim

To investigate the prognostic significance of histone acetylation (HAc) regulators in esophageal cancer (EC) and develop a transcriptome-based HAc_score reflecting epigenetic and immunogenomic states.

Methods

Expression and mutation from EC were analyzed to identify prognostic HAc regulators via univariable Cox models. Consensus clustering defined HAc-related expression patterns. Differentially expressed genes (DEGs) among clusters were functionally enriched. A principal component-based HAc_score was constructed from prognostic DEGs and tested for associations with overall survival, tumor mutational burden (TMB), immunophenoscore (IPS), and immune cell infiltration.

Results

Three HAc-related expression patterns showed distinct biological and immune features. From shared DEGs, 19 prognostic genes defined two molecular subtypes and served as the basis for the HAc_score. Higher HAc_score was associated with better overall survival, particularly in early-stage disease. HAc_score correlated inversely with TMB and positively with IPS components, suggesting a transcriptionally active, immunogenic phenotype despite lower mutation burden. Combining HAc_score with TMB improved risk stratification.

Conclusion

HAc_score quantifies HAc–linked transcriptional states in EC and reflects tumor–immune interactions. It stratifies survival risk and complements TMB, supporting its potential use as a prognostic biomarker and integrative epigenetic–immune signature.