Chromatin regulator expression patterns predict prognosis and guide neoadjuvant therapy in esophageal squamous cell carcinoma.

Chromatin regulators (CRs), as key components of the epigenetic machinery, participate in tumor progression and therapeutic resistance by modulating chromatin structure and gene expression. Nonetheless, the precise functions of CRs in cancer immunotherapy and the tumor microenvironment (TME) remain largely unexplored. Here, we integrated multi-omics data to characterize genomic alterations, transcriptomic profiles, and copy number variations (CNVs) of 215 CRs and identified survival-associated CRs using Cox regression analysis. Subsequently, based on CR expression patterns, esophageal squamous cell carcinoma (ESCC) patients were classified into CR-active and CR-silent subgroups, which exhibited distinct survival outcomes and TME characteristics. Importantly, the CR-Score developed here was associated with treatment response-related endpoints and post-treatment disease-free survival in patients receiving neoadjuvant PD-1 blockade therapy. In summary, we systematically characterized the molecular and immune features of CR clusters in ESCC and demonstrated that the CR-Score is a novel biomarker for prognostic prediction, with potential clinical utility and theoretical relevance for neoadjuvant immunotherapy.