{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T11:49:18Z","timestamp":1775216958614,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T00:00:00Z","timestamp":1775174400000},"content-version":"vor","delay-in-days":92,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"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":["Mediators of Inflammation"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Thyroid carcinoma is characterized by significant heterogeneity and immune evasion, in which myeloid cells play a pivotal role in tumor microenvironment (TME) remodeling. However, the key regulatory genes and their underlying mechanisms are not yet fully elucidated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>This study aims to identify and validate critical myeloid\u2010derived genes involved in driving thyroid cancer progression by employing an integrated multiomics approach.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We performed single\u2010cell RNA sequencing (scRNA\u2010seq) on thyroid cancer tissues, integrated with High\u2010dimensional weighted gene co\u2010expression network analysis (hdWGCNA) for coexpression module identification, Mendelian randomization (MR) for causal inference, and functional validation assays in thyroid carcinoma cell lines including qPCR, CCK\u20108, colony formation, and transwell assays. Microbial correlation analysis and molecular docking were additionally conducted to explore potential interactions.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      We identified a tumor\u2010specific myeloid subpopulation (C5) and a disease\u2010associated coexpression module harboring three hub genes:\n                      <jats:italic>MERTK<\/jats:italic>\n                      ,\n                      <jats:italic>MSR1<\/jats:italic>\n                      , and\n                      <jats:italic>TNFSF12<\/jats:italic>\n                      . MR analysis confirmed\n                      <jats:italic>MERTK<\/jats:italic>\n                      and\n                      <jats:italic>MSR1<\/jats:italic>\n                      as genetic risk factors for thyroid cancer progression, whereas\n                      <jats:italic>TNFSF12<\/jats:italic>\n                      exhibited protective effects. Functional experiments demonstrated that\n                      <jats:italic>TNFSF12<\/jats:italic>\n                      enhances proliferative, invasive, and migratory capacities in thyroid cancer cells. Furthermore,\n                      <jats:italic>MSR1<\/jats:italic>\n                      and\n                      <jats:italic>MERTK<\/jats:italic>\n                      were found to be significantly correlated with specific intratumoral microbiota and associated with BRAF mutation and response to immunotherapy.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      Our study reveals a myeloid\u2010centered regulatory network in thyroid cancer and highlights\n                      <jats:italic>TNFSF12<\/jats:italic>\n                      as a context\u2010dependent oncogene, offering novel insights into targeted therapy and immunotherapeutic strategies.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1155\/mi\/4753653","type":"journal-article","created":{"date-parts":[[2026,4,3]],"date-time":"2026-04-03T10:55:06Z","timestamp":1775213706000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Investigating the Role of\n                    <i>TNFSF12<\/i>\n                    in Thyroid Cancer Progression via Single\u2010Cell RNA Sequencing and Integrated Multiomics 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