{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T06:08:45Z","timestamp":1788761325357,"version":"build-2803163510"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,9,6]],"date-time":"2026-09-06T00:00:00Z","timestamp":1788652800000},"content-version":"vor","delay-in-days":5,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BioFactors"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Lung adenocarcinoma (LUAD) is characterized by marked cellular heterogeneity, yet how malignant epithelial states contribute to immune regulation and clinical outcomes remains incompletely defined. We integrated single\u2010cell RNA\u2010sequencing data to map the cellular landscape of LUAD and identify malignant epithelial cells based on inferred copy\u2010number alterations. Epithelial states were further examined through trajectory inference, transcription factor analysis, and cell\u2013cell communication profiling. Single\u2010cell\u2010derived genes were subsequently integrated with TCGA and independent GEO cohorts to construct and validate a machine learning\u2010based prognostic signature. Malignant epithelial cells displayed distinct functional programs, including an immune\u2010like state associated with genomic instability, immune\u2010related transcriptional activity, tumor\u2013immune communication, and patient outcomes. The resulting immune\u2010like malignant epithelial cell signature (IMEC\u2010Sig) consistently stratified survival across multiple cohorts. Low IMEC\u2010Sig scores were accompanied by greater immune infiltration, higher immune checkpoint expression, and increased immunophenoscore, whereas high scores were linked to a comparatively immunosuppressive phenotype. Pan\u2010cancer analyses further identified KRT8 as a gene associated with unfavorable prognosis, and functional experiments showed that KRT8 silencing suppressed proliferation, migration, invasion, and colony formation in LUAD cells. Together, these findings connect malignant epithelial heterogeneity with the immune context and clinical outcomes, support IMEC\u2010Sig as a biologically informed prognostic tool, and nominate KRT8 as a potential therapeutic target in LUAD.<\/jats:p>","DOI":"10.1002\/biof.70149","type":"journal-article","created":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T05:42:10Z","timestamp":1788759730000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Immune\u2010Like Malignant Epithelial Programs Shape Tumor\u2013Immune Interactions and Inform Prognostic Stratification in Lung Adenocarcinoma"],"prefix":"10.1002","volume":"52","author":[{"given":"Wei","family":"Zhang","sequence":"first","affiliation":[{"name":"Tianjin Chest Hospital, Tianjin University  Tianjin China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Sheng","sequence":"additional","affiliation":[{"name":"Tianjin Chest 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