Impact of age on genomic alterations and the tumor immune microenvironment in papillary thyroid cancer

in Endocrine-Related Cancer
Authors:
Dominique D Liddy Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

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Zhongyue Zhang University of Florida Health Cancer Center, Gainesville, Florida, USA

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Kalyanee Shirlekar University of Florida Health Cancer Center, Gainesville, Florida, USA

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Zhongping He University of Florida Health Cancer Center, Gainesville, Florida, USA
Department of Biostatistics, University of Florida College of Medicine, Gainesville, Florida, USA

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Kelly M Herremans Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

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Song Han Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

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Jason O Brant University of Florida Health Cancer Center, Gainesville, Florida, USA
Department of Biostatistics, University of Florida College of Medicine, Gainesville, Florida, USA

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Francis D Moore Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

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Steven J Hughes Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

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Aditya S Shirali Department of Surgery, University of Florida College of Medicine, Gainesville, Florida, USA

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https://orcid.org/0000-0002-8132-3391

Correspondence should be addressed to A S Shirali: Aditya.Shirali@surgery.ufl.edu
DOI:
https://doi.org/10.1530/ERC-23-0341
Volume/Issue:
Volume 31: Issue 12
Article Type:
Research Article
Article ID:
e230341
Online Publication Date:
04 Nov 2024
Copyright:
© the author(s) 2024
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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 (T1-2N0M0), Group B (T1-3N1a-1bM0), and Group C (T4NxMx or TxNxM1). Histopathologic subtypes included conventional, follicular-variant, and tall cell variant PTC. Spearman’s rank correlation, ANOVA, t-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 ≥65 years (26% vs 4%, P < 0.0001). Tumor mutational burden increased with increasing age (r = 0.463, P < 0.0001). Increasing age was associated with decreased CD8+ T cells (r = −0.15, P = 0.01) using CIBERSORT and decreased B cells (r = −0.13), CD8+ T cells (r = -0.19), and neutrophils (r = −0.14, P < 0.05) using TIMER. Multivariate regression found that increasing age was independently associated with increased resting NK cells and resting dendritic cells, and decreased naïve B cells and CD8+ T cells (P < 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.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2024
Article ID:
e230341
Received Date:
05 Dec 2023
Accepted Date:
24 Sep 2024
Print Publication Date:
01 Dec 2024
Online Publication Date:
04 Nov 2024
Keywords:
computational analysis; genomic alterations; immune cell infiltrate; papillary thyroid carcinoma; tumor immune microenvironment

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