Transcriptomic Differences in Medullary Thyroid Carcinoma According to Grade.
DLL3
Endocrine pathology
Medullary thyroid carcinoma
Neuroendocrine neoplasia
Thyroid
Transcriptomic
Journal
Endocrine pathology
ISSN: 1559-0097
Titre abrégé: Endocr Pathol
Pays: United States
ID NLM: 9009288
Informations de publication
Date de publication:
03 Jul 2024
03 Jul 2024
Historique:
accepted:
25
06
2024
medline:
3
7
2024
pubmed:
3
7
2024
entrez:
3
7
2024
Statut:
aheadofprint
Résumé
Medullary thyroid carcinoma (MTC) is a rare cancer derived from neuroendocrine C-cells of the thyroid. In contrast to other neuroendocrine tumors, a histological grading system was lacking until recently. A novel two-tier grading system based on the presence of high proliferation or necrosis is associated with prognosis. Transcriptomic analysis was conducted on 21 MTCs, including 9 high-grade tumors, with known mutational status, using the NanoString Tumor Signaling 360 Panel. This analysis, covering 760 genes, revealed upregulation of the genes EGLN3, EXO1, UBE2T, UBE2C, FOXM1, CENPA, DLL3, CCNA2, SOX2, KIF23, and CDCA5 in high-grade MTCs. Major pathways differentially expressed between high-grade and low-grade MTCs were DNA damage repair, p53 signaling, cell cycle, apoptosis, and Myc signaling. Validation through qRT-PCR in 30 MTCs demonstrated upregulation of ASCL1, DLL3, and SOX2 in high-grade MTCs, a gene signature akin to small-cell lung carcinoma, molecular subgroup A. Subsequently, DLL3 expression was validated by immunohistochemistry. MTCs with DLL3 overexpression (defined as ≥ 50% of positive tumor cells) were associated with significantly lower disease-free survival (p = 0.041) and overall survival (p = 0.01). Moreover, MTCs with desmoplasia had a significantly increased expression of DLL3. Our data supports the idea that DLL3 should be further explored as a predictor of aggressive disease and poor outcomes in MTC.
Identifiants
pubmed: 38958823
doi: 10.1007/s12022-024-09817-0
pii: 10.1007/s12022-024-09817-0
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Organisme : Instituto Ramón y Cajal de Investigación Sanitaria
ID : 2021/0453
Informations de copyright
© 2024. The Author(s).
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