{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:47:10Z","timestamp":1776919630894,"version":"3.51.2"},"reference-count":48,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Mendelian randomization identified adenosine deaminase as a potential risk factor for esophageal cancer (OR = 1.23, 95% CI: 1.00\u20131.52). 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 \u201cproteasome\u201d and \u201cprotein folding.\u201d 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>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.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fmolb.2026.1798177","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:22:14Z","timestamp":1776918134000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the role of adenosine deaminase in esophageal cancer and its potential for traditional Chinese medicine intervention"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaoling","family":"Tian","sequence":"first","affiliation":[{"name":"Baotou Medical College, Inner Mongolia University of Science and Technology","place":["Baotou, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhong","family":"Liu","sequence":"additional","affiliation":[{"name":"Baotou Medical College, Inner Mongolia University of Science and Technology","place":["Baotou, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Baochun","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Binzhou Polytechnic","place":["Binzhou, Shandong, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yubo","family":"Liu","sequence":"additional","affiliation":[{"name":"Baotou Medical College, Inner Mongolia University of Science and Technology","place":["Baotou, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fengqi","family":"Liu","sequence":"additional","affiliation":[{"name":"Baotou Medical College, Inner Mongolia University of Science and Technology","place":["Baotou, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chenlin","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of oncology, Baotou Cancer Hospital","place":["Baotou, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuang","family":"Lv","sequence":"additional","affiliation":[{"name":"Department of oncology, Baotou Cancer Hospital","place":["Baotou, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yunqi","family":"Hua","sequence":"additional","affiliation":[{"name":"Department of oncology, Baotou Cancer Hospital","place":["Baotou, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fangrui","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, The First Affiliated Hospital of Baotou Medical College","place":["Baotou, Inner Mongolia, China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/s41571-020-0382-2","article-title":"The adenosine pathway in immuno-oncology","volume":"17","author":"Allard","year":"2020","journal-title":"Nat. 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