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Identification of Specific Biomarkers for Anaplastic Thyroid Carcinoma Through Spatial Transcriptomic and
Faridul Haq1,2,3, Andrey Bychkov4, Ozgur Mete5
1Department of Hospital Pathology, College of Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero, Seocho-Gu, Seoul, 06591, Republic of Korea.
Endocrine Pathology
|April 17, 2025
Summary
This study identified eight molecular markers that can distinguish aggressive anaplastic thyroid carcinoma (ATC) from other thyroid tumors. These validated mRNA and protein markers are independent of BRAF mutation status, aiding ATC diagnosis.
Area of Science:
- Oncology
- Molecular Pathology
- Genomics
Background:
- Anaplastic thyroid carcinoma (ATC) is a rare but aggressive malignancy with a poor prognosis.
- Distinguishing ATC from other thyroid carcinomas is crucial for effective treatment.
- Identifying reliable molecular markers for ATC diagnosis and characterization is needed.
Purpose of the Study:
- To identify and validate key mRNA and protein markers for distinguishing ATC from other thyroid tumors.
- To assess the association of these markers with tumor progression and dedifferentiation.
- To evaluate the impact of BRAF p.V600E mutation status on marker expression.
Main Methods:
- Spatial transcriptomic analysis on an ATC and papillary thyroid carcinoma (PTC) coexisting case.
- Validation of differentially expressed mRNA markers using immunohistochemistry on a large cohort of various thyroid tumor types.
- Evaluation of BRAF p.V600E mutation status in relation to marker expression.
Main Results:
- Eight differentially expressed mRNA markers were identified: COL7A1, LAMC2, SPHK1, SRPX2 (overexpressed) and CD24, EPHX1, GPX3, RBM47 (downregulated) in ATCs.
- Overexpression of COL7A1, LAMC2, SPHK1, and SRPX2, and downregulation of CD24, EPHX1, GPX3, and RBM47 were validated at both mRNA and protein levels in ATCs.
- Functional enrichment analysis indicated roles in tumor invasion, epithelial-mesenchymal transition, extracellular matrix remodeling, and immune evasion.
- Marker expression was independent of BRAF p.V600E mutation status.
Conclusions:
- This study successfully identified and validated eight molecular markers capable of differentiating ATC from other thyroid tumors.
- The validated markers hold significant clinical relevance for the diagnosis and characterization of ATC.
- These findings provide a basis for developing future biomarker-driven diagnostic and therapeutic strategies for ATC.
