{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:43:31Z","timestamp":1792190611235,"version":"4.4.0"},"reference-count":43,"publisher":"Bioscientifica","issue":"12","content-domain":{"domain":["erc.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,9,24]]},"abstract":"\n Differentiated thyroid cancer in older adults has been linked to alterations in the mutational landscape and tumor immune cell infiltration that create a tumor-permissive microenvironment. We sought to determine the impact of age on genomic alterations and immune cell composition in papillary thyroid cancer (PTC). Genomic alterations, immune cell composition, and clinical data were obtained using The Cancer Genome Atlas and computational immunogenomic analyses. Disease severity was recoded into three groups: Group A (T\n 1-2<\/jats:sub>\n N\n 0<\/jats:sub>\n M\n 0<\/jats:sub>\n ), Group B (T\n 1-3<\/jats:sub>\n N\n 1a-1b<\/jats:sub>\n M\n 0<\/jats:sub>\n ), and Group C (T\n 4<\/jats:sub>\n N\n x<\/jats:sub>\n M\n x<\/jats:sub>\n or T\n x<\/jats:sub>\n N\n x<\/jats:sub>\n M\n 1<\/jats:sub>\n ). Histopathologic subtypes included conventional, follicular-variant, and tall cell variant PTC. Spearman\u2019s rank correlation, ANOVA,\n t<\/jats:italic>\n -test, and multivariable linear regression were performed. A total of 470 PTC samples were retrieved from the TCGA portal with genomic alteration and immune cell composition data. TERT promoter alterations were more common in patients aged \u226565 years (26% vs 4%,\n P<\/jats:italic>\n < 0.0001). Tumor mutational burden increased with increasing age (\n r<\/jats:italic>\n = 0.463,\n P<\/jats:italic>\n < 0.0001). Increasing age was associated with decreased CD8+ T cells (\n r<\/jats:italic>\n \u2009=\u2009\u22120.15,\n P<\/jats:italic>\n \u2009=\u20090.01) using CIBERSORT and decreased B cells (\n r<\/jats:italic>\n \u2009=\u2009\u22120.13), CD8+ T cells (\n r<\/jats:italic>\n \u2009=\u2009-0.19), and neutrophils (\n r<\/jats:italic>\n \u2009=\u2009\u22120.14,\n P<\/jats:italic>\n < 0.05) using TIMER. Multivariate regression found that increasing age was independently associated with increased resting NK cells and resting dendritic cells, and decreased na\u00efve B cells and CD8+ T cells (\n P<\/jats:italic>\n < 0.05). PTC tumors of older adults are characterized by increased TERT promoter alterations, increased tumor mutational burden, and a decreased cytotoxic CD8+ T cells and increased resting dendritic cell immune infiltrate. Further studies are needed to determine if these changes in immune cell infiltrate are associated with compromised outcomes.\n <\/jats:p>","DOI":"10.1530\/erc-23-0341","type":"journal-article","created":{"date-parts":[[2024,9,24]],"date-time":"2024-09-24T10:15:08Z","timestamp":1727172908000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":8,"title":["Impact of age on genomic alterations and the tumor immune microenvironment in papillary thyroid cancer"],"prefix":"10.1530","volume":"31","author":[{"given":"Dominique D","family":"Liddy","sequence":"first","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongyue","family":"Zhang","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Center, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kalyanee","family":"Shirlekar","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Center, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongping","family":"He","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Center, Gainesville, Florida, USA"},{"name":"Department of Biostatistics, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly M","family":"Herremans","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song","family":"Han","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason O","family":"Brant","sequence":"additional","affiliation":[{"name":"University of Florida Health Cancer Center, Gainesville, Florida, USA"},{"name":"Department of Biostatistics, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francis D","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven J","family":"Hughes","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8132-3391","authenticated-orcid":true,"given":"Aditya S","family":"Shirali","sequence":"additional","affiliation":[{"name":"Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"bib1","series-title":"Journal of Clinical Oncology","first-page":"4415","article-title":"Exploring the relationship between patient age and cancer-specific survival in papillary thyroid cancer: rethinking current staging systems","volume":"34","author":"Adam","year":"2016","unstructured":"Adam MAThomas SHyslop TScheri RPRoman SA & Sosa JA 2016 Exploring the relationship between patient age and cancer-specific survival in papillary thyroid cancer: rethinking current staging systems. 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