{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T09:21:12Z","timestamp":1787822472819,"version":"build-2784847793"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Esophageal squamous cell carcinoma (ESCC) features epithelial heterogeneity and an immunosuppressive microenvironment, yet clinically relevant malignant epithelial states remain poorly defined. We integrated four single\u2010cell RNA\u2010sequencing datasets and 10 bulk transcriptomic cohorts totaling 1318 samples, and applied cross\u2010cohort differential expression, survival analysis, and a machine\u2010learning framework of 113 algorithm combinations to screen for malignant epithelial cell\u2010associated biomarkers. GNGT1 was prioritized for its consistent upregulation, prognostic association, and limited prior characterization in ESCC. Across independent cohorts, GNGT1 exhibited favorable diagnostic performance, while high expression correlated with poorer overall survival and more advanced local tumor status. Immune deconvolution consistently linked GNGT1\u2010high tumors to reduced CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell infiltration, lower immune scores, and decreased cytotoxic T\u2010cell markers. Single\u2010cell analyses further associated GNGT1\u2010high epithelial cells with altered epithelial\u2013immune communication involving MIF, prostaglandin, and CXCL signaling, alongside enrichment of epithelial\u2013mesenchymal transition, mTORC1, and proliferative programs; qPCR confirmed elevated GNGT1 expression in ESCC cell lines. This study defines GNGT1 as a marker of an immunosuppressive malignant epithelial state, thereby bridging epithelial heterogeneity with immune remodeling in ESCC. These findings support GNGT1 as a candidate diagnostic, prognostic, and biologically informative biomarker warranting mechanistic and clinical validation.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70381","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T04:54:21Z","timestamp":1786596861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Single\u2010Cell and Bulk Transcriptomics Identify\n                    <scp>GNGT1<\/scp>\n                    \u2010High Malignant Epithelial Cells Associated With Immune Suppression in Esophageal Squamous Cell Carcinoma"],"prefix":"10.1111","volume":"108","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0496-8831","authenticated-orcid":false,"given":"Qian","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery Second Affiliated Hospital of Naval Medical University  Shanghai 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