1. Gene Expression Profiles of AHNAK2, DCSTAMP, FN1, and TERT Correlate With Mutational Status and Recurrence in Papillary Thyroid Carcinoma.
- Author
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Staubitz-Vernazza JI, Müller C, Heymans A, Nedwed AS, Schindeldecker M, Hartmann M, Kloth M, Schad A, Roth W, Musholt TJ, and Hartmann N
- Subjects
- Humans, Female, Male, Middle Aged, Adult, Proto-Oncogene Proteins B-raf genetics, Membrane Proteins genetics, Aged, Transcriptome, Biomarkers, Tumor genetics, Gene Expression Regulation, Neoplastic, Promoter Regions, Genetic, Cytoskeletal Proteins, Fibronectins, Telomerase genetics, Mutation, Thyroid Cancer, Papillary genetics, Thyroid Cancer, Papillary pathology, Neoplasm Recurrence, Local genetics, Neoplasm Recurrence, Local pathology, Thyroid Neoplasms genetics, Thyroid Neoplasms pathology
- Abstract
Papillary thyroid carcinoma (PTC), the most common malignancy of follicular cell derivation, is generally associated with good prognosis. Nevertheless, it is important to identify patients with aggressive PTCs and unfavorable outcome. Molecular markers such as BRAF
V600E mutation and TERT promoter mutations have been proposed for risk stratification. While TERT promoter mutations have been frequently associated with aggressive PTCs, the association of BRAFV600E mutation with increased recurrence and mortality is less clear and has been controversially discussed. The aim of the present study was to analyze whether differentially expressed genes can predict BRAFV600E mutations as well as TERT promoter mutations in PTCs. RNA sequencing identified a large number of differentially expressed genes between BRAFV600E and BRAFwildtype PTCs. Of those, AHNAK2, DCSTAMP, and FN1 could be confirmed in a larger cohort (n = 91) to be significantly upregulated in BRAFV600E mutant PTCs using quantitative RT-PCR. Moreover, individual PTC expression values of DCSTAMP and FN1 were able to predict the BRAFV600E mutation status with high sensitivity and specificity. The expression of TERT was detected in all PTCs harboring TERT promoter mutations and in 19% of PTCs without TERT promoter mutations. Tumors with both TERT expression and TERT promoter mutations were particularly associated with aggressive clinicopathological features and a shorter recurrence-free survival. Altogether, it will be interesting to explore the biological function of AHNAK2, DCSTAMP, and FN1 in PTC in more detail. The analysis of their expression patterns could allow the characterization of PTC subtypes and thus enabling a more individualized surgical and medical treatment., (© 2024 The Author(s). Genes, Chromosomes and Cancer published by Wiley Periodicals LLC.)- Published
- 2024
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