Promoter mutation-independent TERT expression is related to the immune-enriched milieu in papillary thyroid cancer

in Endocrine-Related Cancer
Authors:
Dong Hyun Seo Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

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Seul Gi Lee Yonsei University Graduate School of Medical Science, Seoul, South Korea

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Soon Min Choi Department of Surgery, Hallym Hospital, Incheon, South Korea

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Ha Yan Kim Biostatistics Collaboration Unit, Department of Biomedical Systems Informatics, Yonsei University College of Medicine, Seoul, South Korea

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Sunmi Park Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

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Sang Geun Jung Department of Gynecological Oncology, Bundang CHA Medical Center, CHA University Gyeonggi-do, South Korea

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Young Suk Jo Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea

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https://orcid.org/0000-0001-9926-8389
, and
Jandee Lee Department of Surgery, Open NBI Convergence Technology Research Laboratory, Yonsei University College of Medicine, Seoul, South Korea

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Correspondence should be addressed to YS Jo or J Lee: joys@yuhs.ac or jandee@yuhs.ac

*(D H Seo, S G Lee and S M Choi contributed equally to this work)

DOI:
https://doi.org/10.1530/ERC-24-0068
Volume/Issue:
Volume 31: Issue 11
Article Type:
Research Article
Article ID:
e240068
Online Publication Date:
07 Oct 2024
Copyright:
© the author(s) 2024
Restricted access
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Telomerase reverse transcriptase promoter mutation (pTERT MT) promotes human carcinogenesis via aberrant expression of telomerase reverse transcriptase (TERT). However, the tumorigenic impact of TERT expression independent of pTERT MT remains unclear despite numerous mechanisms of TERT being suggested. To tackle this issue, we employed comprehensive bioinformatics to assess biological variations noticed among different TERT expression mechanisms. Papillary thyroid cancer (PTC) with pTERT MT (pTERT MT PTC) presented aggressive clinical behavior and exhibited biological profiles associated with cellular immortality and genomic instability. PTC with TERT expression but without pTERT MT (TERT (+) PTC), also exhibited poor clinicopathological characteristics and was enriched with immune responses. In accordance, c-MYC/E2F and nuclear factor kappa B (NFκB) were dominant transcription factors in pTERT MT PTC and TERT (+) PTC, respectively. Notably, we revealed TERT hypermethylated oncological region (THOR) as a potential TERT expressing mechanism in TERT (+) PTC patients. Furthermore, three unique subtypes of papillary thyroid cancer were deciphered using a combination of machine learning-based scoring systems. Our proposed scoring system was clinically significant, especially in microcarcinoma, predicting survival outcomes and inferring therapeutic responses to radioactive iodine therapy. Finally, our analysis was expanded to endocrine-related cancers, unveiling various regulatory mechanisms of TERT with poor clinical outcomes and biological behaviors.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2024
Article ID:
e240068
Received Date:
03 Apr 2024
Accepted Date:
22 Aug 2024
Print Publication Date:
01 Nov 2024
Online Publication Date:
07 Oct 2024
Keywords:
DNA methylation; GSEA; immune response; MYC; NFκB; papillary thyroid cancer; replication; TERT; TERT hypermethylated oncological region

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