{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:25:37Z","timestamp":1787117137843,"version":"build-2736575974"},"reference-count":24,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"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. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Efferocytosis, the clearance of apoptotic cells by phagocytes, contributes to immune homeostasis but may also promote tumor immune tolerance. However, its transcriptional landscape and clinical relevance in lung adenocarcinoma (LUAD) remain incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically analyzed efferocytosis-associated genes across TCGA and multiple GEO datasets to classify LUAD subtypes and construct a prognostic risk model. The prognostic and immunological relevance of this model was validated in four independent cohorts and further assessed through immune infiltration, genomic, and immunotherapy datasets. Functional and pharmacogenomic analyses were performed to identify potential therapeutic vulnerabilities, and the efferocytosis-associated signature gene\n                      <jats:italic>KCTD12<\/jats:italic>\n                      was subsequently validated\n                      <jats:italic>in vitro.<\/jats:italic>\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Unsupervised clustering identified two efferocytosis-based LUAD subtypes with distinct prognostic and immune\u2013metabolic characteristics. The derived risk model robustly predicted overall survival across validation cohorts. Among the model genes, KCTD12 emerged as an efferocytosis-associated candidate linked to an immune-active tumor microenvironment. Across the analyzed single-cell, spatial transcriptomic, and immunotherapy-treated cohorts, higher KCTD12 expression was associated with enhanced cytotoxic T-cell activity and more favorable treatment outcomes. Functional experiments confirmed that KCTD12 suppresses tumor cell proliferation, reduces colony formation, and enhances OT-1 CD8\n                      <jats:sup>+<\/jats:sup>\n                      T-cell activation and cytotoxicity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our study identifies an efferocytosis-associated transcriptional program linked to immune heterogeneity and prognosis in LUAD. The efferocytosis-related risk signature provides a framework for prognostic and immune stratification, while KCTD12 represents a candidate biomarker associated with immune activation and clinical outcomes in immunotherapy-treated cohorts. Its treatment-specific predictive value requires prospective validation in appropriately controlled studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1930176","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T04:41:35Z","timestamp":1787114495000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efferocytosis related KCTD12 is a clinico-immune target in lung adenocarcinoma"],"prefix":"10.3389","volume":"16","author":[{"given":"Wen","family":"Shan","sequence":"first","affiliation":[{"name":"Department of Thoracic Surgery and Cardiac Surgery, The Second People\u2019s Hospital of Fuyang City","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanya","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Cardiac Surgery, The Second People\u2019s Hospital of Fuyang City","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Thoracic Surgery and Cardiac Surgery, The Second People\u2019s Hospital of Fuyang City","place":["Fuyang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yifei","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center","place":["Shanghai, China"]},{"name":"Department of Oncology, Shanghai Medical College, Fudan University","place":["Shanghai, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 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