{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:43:16Z","timestamp":1792190596236,"version":"4.4.0"},"reference-count":39,"publisher":"SAGE Publications","issue":"4","license":[{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,4,1]],"date-time":"2025-04-01T00:00:00Z","timestamp":1743465600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Thyroid\u00ae"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>Although patients with anaplastic thyroid cancer (ATC) generally have a poor prognosis and there are currently no effective treatment options, survival and response to therapy vary between patients. Genomic and transcriptomic profiles of ATC have been reported; however, a comprehensive study of the tumor microenvironment (TME) of ATC is still lacking. This study aimed to elucidate the TME characteristics associated with ATC and their prognostic implications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>\n                      We analyzed bulk RNA transcriptomic data from 1,634 samples\u2014including 476 normal thyroid tissues, 25 benign thyroid adenomas, 340\n                      <jats:italic toggle=\"yes\">RAS<\/jats:italic>\n                      -like and 719\n                      <jats:italic toggle=\"yes\">BRAF<\/jats:italic>\n                      <jats:sup>V600E<\/jats:sup>\n                      -like differentiated thyroid cancers (DTC-R and DTC-B, respectively), and 74 ATCs. We assessed the TME and molecular characteristics of these thyroid cancer subtypes using deconvolution analysis.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>\n                      The TME of ATC was characterized by a high abundance of immune cells and fibroblasts and a low abundance of epithelial cells compared to other thyroid histologies. During its malignant evolution, ATC exhibited an ecotype more closely related to DTC-B than\n                      <jats:italic toggle=\"yes\">RAS<\/jats:italic>\n                      -like DTC (DTC-R). Furthermore, we identified two distinct molecular subtypes within ATC with significant differences in their TMEs. We termed the subtype with increased immune cells and fibroblasts as ATC-immune-fibroblast (ATC-IF) and the subtype with elevated epithelial and endothelial cells as ATC-epithelial-endothelial (ATC-E). The ATC-IF group had worse disease-specific survival (log-rank\n                      <jats:italic toggle=\"yes\">p<\/jats:italic>\n                      = 0.035), higher ERK scores, and lower thyroid differentiation scores than the ATC-E group. While both ATC subtypes had elevated immune cells and fibroblasts compared to DTC-R and DTC-B, this increase was more pronounced in ATC-IF, with a marked rise in myeloid lineage cells and promigratory fibroblasts. Immune checkpoint gene expression and epithelial\u2013mesenchymal transition scores were significantly higher in the ATC-IF group than in the ATC-E group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>ATC shows a TME distinct from that of DTC and can be further divided into two molecular subtypes\u2014each with its own unique TME. The ATC-IF group, with a poorer prognosis and higher ERK score, is enriched in immune cells and fibroblasts, which may represent potential therapeutic targets.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1089\/thy.2024.0266","type":"journal-article","created":{"date-parts":[[2025,1,27]],"date-time":"2025-01-27T10:24:08Z","timestamp":1737973448000},"page":"367-378","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":21,"title":["Transcriptome of Anaplastic Thyroid Cancer Reveals Two Molecular Subtypes with Distinct Tumor Microenvironment and Prognosis"],"prefix":"10.1177","volume":"35","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1704-5013","authenticated-orcid":false,"given":"Hyunjong","family":"Byun","sequence":"first","affiliation":[{"name":"CHA University School of Medicine, Pocheon, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6337-0162","authenticated-orcid":false,"given":"Han Sai","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Gwanak-gu, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4603-1999","authenticated-orcid":false,"given":"Young Shin","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul National University College of Medicine, Dongjak-gu, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3671-6364","authenticated-orcid":false,"given":"Young Joo","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Gwanak-gu, Republic of Korea."},{"name":"Department of Internal Medicine and Genomic Medicine Institute, Medical Research Center, Seoul National University College of Medicine, Jongno-gu, Republic of Korea."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2025,4,15]]},"reference":[{"key":"e_1_3_7_2_2","first-page":"10756","volume-title":"Harrison\u2019s Principles of Internal Medicine","author":"Jameson JL","year":"2022","unstructured":"Jameson JL, , Mandel SJ, , Weetman AP, et al. Thyroid nodular disease and thyroid cancer. In: Harrison\u2019s Principles of Internal Medicine. (Loscalzo J, , Fauci AS, , Kasper DL eds.) United States of: McGraw Hill LLC; 2022; pp. 10756\u201310769."},{"key":"e_1_3_7_3_2","volume-title":"Tumors of the Thyroid Gland","author":"Rosai J","year":"1992","unstructured":"Rosai J, , Carcangiu M, , DeLellis R.3rd., Tumors of the Thyroid Gland. 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