ADAP2 drives immune-associated progression of esophageal cancer and serves as a potential therapeutic target

Esophageal cancer (EC) remains a highly aggressive malignancy with poor prognosis, and the efficacy of current therapeutic strategies, including immunotherapy, is limited by substantial heterogeneity. Identifying immune-associated molecular drivers that contribute to EC progression may facilitate the development of effective targeted therapies.

An integrated transcriptomic analysis was performed using TCGA-EC datasets to characterize immune-related gene networks associated with the tumor microenvironment. Weighted gene co-expression network analysis and differential expression analysis were applied to identify immune-associated candidate genes. A prognostic model was constructed and evaluated using regression analyses. Functional roles of the key candidate gene ADAP2 were further investigated through in vitro assays assessing proliferation and migration, as well as in vivo xenograft models to evaluate tumor growth.

Immune-related gene modules were strongly correlated with immune and stromal components of the EC microenvironment and were enriched in pathways involved in immune regulation and intercellular signaling. A multi-gene prognostic signature stratified EC patients into distinct risk groups with significantly different survival outcomes. Among these genes, ADAP2 emerged as a central immune-associated factor. Functional experiments demonstrated that ADAP2 markedly promoted EC cell proliferation and migratory capacity in vitro. Consistently, xenograft models confirmed that ADAP2 overexpression significantly accelerated tumor growth in vivo.

This study integrates immune transcriptomic profiling with functional validation to identify ADAP2 as a key driver of EC progression.