Transcriptomic Analysis of Papillary Thyroid Cancer: A Focus on Immune-Subtyping, Oncogenic Fusion, and Recurrence

Seung-Jin Park; Yea Eun Kang; Jeong-Hwan Kim; Jong-Lyul Park; Seon-Kyu Kim; Seung-Woo Baek; In Sun Chu; Shinae Yi; Seong Eun Lee; Young Joo Park; Eun-Jae Chung; Jin Man Kim; Hye Mi Ko; Je-Ryong Kim; Seung-Nam Jung; Ho-Ryun Won; Jae Won Chang; Bon Seok Koo; Seon-Young Kim

doi:10.21053/ceo.2021.02215

Clinical and Experimental Otorhinolaryngology (May 2022)

Transcriptomic Analysis of Papillary Thyroid Cancer: A Focus on Immune-Subtyping, Oncogenic Fusion, and Recurrence

Seung-Jin Park,
Yea Eun Kang,
Jeong-Hwan Kim,
Jong-Lyul Park,
Seon-Kyu Kim,
Seung-Woo Baek,
In Sun Chu,
Shinae Yi,
Seong Eun Lee,
Young Joo Park,
Eun-Jae Chung,
Jin Man Kim,
Hye Mi Ko,
Je-Ryong Kim,
Seung-Nam Jung,
Ho-Ryun Won,
Jae Won Chang,
Bon Seok Koo,
Seon-Young Kim

Affiliations

Seung-Jin Park: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Yea Eun Kang: Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
Jeong-Hwan Kim: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Jong-Lyul Park: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Seon-Kyu Kim: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Seung-Woo Baek: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
In Sun Chu: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea
Shinae Yi: Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
Seong Eun Lee: Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Korea
Young Joo Park: Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea
Eun-Jae Chung: Department of Otorhinolaryngology-Head and Neck Surgery, Seoul National University College of Medicine, Seoul, Korea
Jin Man Kim: Department of Pathology, Chungnam National University College of Medicine, Daejeon, Korea
Hye Mi Ko: Department of Surgery, Chungnam National University College of Medicine, Daejeon, Korea
Je-Ryong Kim: Department of Surgery, Chungnam National University College of Medicine, Daejeon, Korea
Seung-Nam Jung: Department of Otolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Korea
Ho-Ryun Won: Department of Otolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Korea
Jae Won Chang: Department of Otolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Korea
Bon Seok Koo: Department of Otolaryngology-Head and Neck Surgery, Chungnam National University College of Medicine, Daejeon, Korea
Seon-Young Kim: Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea

DOI: https://doi.org/10.21053/ceo.2021.02215
Journal volume & issue: Vol. 15, no. 2
pp. 183 – 193

Abstract

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Objectives Thyroid cancer is the most common endocrine tumor, with rapidly increasing incidence worldwide. However, its transcriptomic characteristics associated with immunological signatures, driver fusions, and recurrence markers remain unclear. We aimed to investigate the transcriptomic characteristics of advanced papillary thyroid cancer. Methods This study included 282 papillary thyroid cancer tumor samples and 155 normal samples from Chungnam National University Hospital and Seoul National University Hospital. Transcriptomic quantification was determined by high-throughput RNA sequencing. We investigated the associations of clinical parameters and molecular signatures using RNA sequencing. We validated predictive biomarkers using the Cancer Genome Atlas database. Results Through a comparison of differentially expressed genes, gene sets, and pathways in papillary thyroid cancer compared to normal tumor-adjacent tissue, we found increased immune signaling associated with cytokines or T cells and decreased thyroid hormone synthetic pathways. In addition, patients with recurrence presented increased CD8+ T-cell and Th1-cell signatures. Interestingly, we found differentially overexpressed genes related to immune-escape signaling such as CTLA4, IDO1, LAG3, and PDCD1 in advanced papillary thyroid cancer with a low thyroid differentiation score. Fusion analysis showed that the PI3K and mitogen-activated protein kinase (MAPK) signaling pathways were regulated differently according to the RET fusion partner genes (CCDC6 or NCOA4). Finally, we identified HOXD9 as a novel molecular biomarker that predicts the recurrence of thyroid cancer in addition to known risk factors (tumor size, lymph node metastasis, and extrathyroidal extension). Conclusion We identified a high association with immune-escape signaling in the immune-hot group with aggressive clinical characteristics among Korean thyroid cancer patients. Moreover, RET fusion differentially regulated PI3K and MAPK signaling depending on the partner gene of RET, and HOXD9 was found to be a recurrence marker for advanced papillary thyroid cancer.

Published in Clinical and Experimental Otorhinolaryngology

ISSN: 1976-8710 (Print); 2005-0720 (Online)
Publisher: Korean Society of Otorhinolaryngology-Head and Neck Surgery
Country of publisher: Korea, Republic of
LCC subjects: Medicine: Otorhinolaryngology
Website: https://www.e-ceo.org/

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