Different Molecular Phenotypes of Progression in - and -Like Papillary Thyroid Carcinoma
Background Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RAS-like (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signat...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Korean Endocrine Society
2023-08-01
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| Series: | Endocrinology and Metabolism |
| Subjects: | |
| Online Access: | http://www.e-enm.org/upload/pdf/enm-2023-1702.pdf |
| _version_ | 1797730946945908736 |
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| author | Jinsun Lim Han Sai Lee Jiyun Park Kyung-Soo Kim Soo-Kyung Kim Yong-Wook Cho Young Shin Song |
| author_facet | Jinsun Lim Han Sai Lee Jiyun Park Kyung-Soo Kim Soo-Kyung Kim Yong-Wook Cho Young Shin Song |
| author_sort | Jinsun Lim |
| collection | DOAJ |
| description | Background Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RAS-like (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. Methods We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. Results Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection-invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. Conclusion The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs. |
| first_indexed | 2024-03-12T11:51:30Z |
| format | Article |
| id | doaj.art-5a8cc9104e434d9fa74cd383e9a089b6 |
| institution | Directory Open Access Journal |
| issn | 2093-596X 2093-5978 |
| language | English |
| last_indexed | 2024-03-12T11:51:30Z |
| publishDate | 2023-08-01 |
| publisher | Korean Endocrine Society |
| record_format | Article |
| series | Endocrinology and Metabolism |
| spelling | doaj.art-5a8cc9104e434d9fa74cd383e9a089b62023-08-31T07:16:44ZengKorean Endocrine SocietyEndocrinology and Metabolism2093-596X2093-59782023-08-0138444545410.3803/EnM.2023.17022405Different Molecular Phenotypes of Progression in - and -Like Papillary Thyroid CarcinomaJinsun Lim0Han Sai Lee1Jiyun Park2Kyung-Soo Kim3Soo-Kyung Kim4Yong-Wook Cho5Young Shin Song6 Department of Medicine, CHA University School of Medicine, Seongnam, Korea Department of Biomedical Science, Graduate School, CHA University, Seongnam, Korea Department of Medicine, CHA University School of Medicine, Seongnam, Korea Department of Medicine, CHA University School of Medicine, Seongnam, Korea Department of Medicine, CHA University School of Medicine, Seongnam, Korea Department of Medicine, CHA University School of Medicine, Seongnam, Korea Department of Medicine, CHA University School of Medicine, Seongnam, KoreaBackground Papillary thyroid carcinoma (PTC) can be classified into two distinct molecular subtypes, BRAF-like (BL) and RAS-like (RL). However, the molecular characteristics of each subtype according to clinicopathological factors have not yet been determined. We aimed to investigate the gene signatures and tumor microenvironment according to clinicopathological factors, and to identify the mechanism of progression in BL-PTCs and RL-PTCs. Methods We analyzed RNA sequencing data and corresponding clinicopathological information of 503 patients with PTC from The Cancer Genome Atlas database. We performed differentially expressed gene (DEG), Gene Ontology, and molecular pathway enrichment analyses according to clinicopathological factors in each molecular subtype. EcoTyper and CIBERSORTx were used to deconvolve the tumor cell types and their surrounding microenvironment. Results Even for the same clinicopathological factors, overlapping DEGs between the two molecular subtypes were uncommon, indicating that BL-PTCs and RL-PTCs have different progression mechanisms. Genes related to the extracellular matrix were commonly upregulated in BL-PTCs with aggressive clinicopathological factors, such as old age (≥55 years), presence of extrathyroidal extension, lymph node metastasis, advanced tumor-node-metastasis (TNM) stage, and high metastasis-age-completeness of resection-invasion-size (MACIS) scores (≥6). Furthermore, in the deconvolution analysis of tumor microenvironment, cancer-associated fibroblasts were significantly enriched. In contrast, in RL-PTCs, downregulation of immune response and immunoglobulin-related genes was significantly associated with aggressive characteristics, even after adjusting for thyroiditis status. Conclusion The molecular phenotypes of cancer progression differed between BL-PTC and RL-PTC. In particular, extracellular matrix and cancer-associated fibroblasts, which constitute the tumor microenvironment, would play an important role in the progression of BL-PTC that accounts for the majority of advanced PTCs.http://www.e-enm.org/upload/pdf/enm-2023-1702.pdfthyroid cancer, papillarytranscriptomegene expression profilingtumor microenvironment |
| spellingShingle | Jinsun Lim Han Sai Lee Jiyun Park Kyung-Soo Kim Soo-Kyung Kim Yong-Wook Cho Young Shin Song Different Molecular Phenotypes of Progression in - and -Like Papillary Thyroid Carcinoma Endocrinology and Metabolism thyroid cancer, papillary transcriptome gene expression profiling tumor microenvironment |
| title | Different Molecular Phenotypes of Progression in - and -Like Papillary Thyroid Carcinoma |
| title_full | Different Molecular Phenotypes of Progression in - and -Like Papillary Thyroid Carcinoma |
| title_fullStr | Different Molecular Phenotypes of Progression in - and -Like Papillary Thyroid Carcinoma |
| title_full_unstemmed | Different Molecular Phenotypes of Progression in - and -Like Papillary Thyroid Carcinoma |
| title_short | Different Molecular Phenotypes of Progression in - and -Like Papillary Thyroid Carcinoma |
| title_sort | different molecular phenotypes of progression in and like papillary thyroid carcinoma |
| topic | thyroid cancer, papillary transcriptome gene expression profiling tumor microenvironment |
| url | http://www.e-enm.org/upload/pdf/enm-2023-1702.pdf |
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