Exploring the role of adenosine deaminase in esophageal cancer and its potential for traditional Chinese medicine intervention.

Introduction: This study aims to systematically elucidate the association of adenosine deaminase with esophageal cancer from a genetic perspective and explore its potential underlying mechanisms and intervention strategies. Methods: Through multi-level integrative analysis, two-sample Mendelian randomization analysis was performed, followed by serum validation in an independent case-control cohort. Transcriptomic analysis, co-expression network enrichment, single-cell RNA sequencing, reverse network pharmacology screening, and molecular docking simulation were conducted. Results: Mendelian randomization identified adenosine deaminase as a potential risk factor for esophageal cancer (OR = 1.23, 95% CI: 1.00-1.52). Significantly elevated serum ADA levels were validated in patients. ADA expression was upregulated in tumor tissues, and its co-expression network was significantly enriched in pathways related to "proteasome" and "protein folding." Single-cell analysis showed high ADA expression primarily in plasma cells and plasmacytoid dendritic cells. Two potential lead compounds, catechin and flavoxanthin, were identified to stably bind to ADA. Discussion: Collectively, these findings suggest a potential role for ADA in the occurrence of esophageal cancer and highlight its possible relevance as a therapeutic target, providing new directions for early intervention and targeted therapy of esophageal cancer.