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.