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Molecular Determinants of Thyroid Nodules with Indeterminate Cytology and RAS Mutations
- Source :
- Thyroid
- Publication Year :
- 2021
- Publisher :
- Mary Ann Liebert, Inc., publishers, 2021.
-
Abstract
- Background: RAS gene family mutations are the most prevalent in thyroid nodules with indeterminate cytology and are present in a wide spectrum of histological diagnoses. We evaluated differentially expressed genes and signaling pathways across the histological/clinical spectrum of RAS-mutant nodules to determine key molecular determinants associated with a high risk of malignancy. Methods: Sixty-one thyroid nodules with RAS mutations were identified. Based on the histological diagnosis and biological behavior, the nodules were grouped into five categories indicating their degree of malignancy: non-neoplastic appearance, benign neoplasm, indeterminate malignant potential, low-risk cancer, or high-risk cancer. Gene expression profiles of these nodules were determined using the NanoString PanCancer Pathways and IO 360 Panels, and Angiopoietin-2 level was determined by immunohistochemical staining. Results: The analysis of differentially expressed genes using the five categories as supervising parameters unearthed a significant correlation between the degree of malignancy and genes involved in cell cycle and apoptosis (BAX, CCNE2, CDKN2A, CDKN2B, CHEK1, E2F1, GSK3B, NFKB1, and PRKAR2A), PI3K pathway (CCNE2, CSF3, GSKB3, NFKB1, PPP2R2C, and SGK2), and stromal factors (ANGPT2 and DLL4). The expression of Angiopoietin-2 by immunohistochemistry also showed the same trend of increasing expression from non-neoplastic appearance to high-risk cancer (p
- Subjects :
- Thyroid nodules
Adult
Male
Pathology
medicine.medical_specialty
Adolescent
Endocrinology, Diabetes and Metabolism
Biology
Angiopoietin-2
Young Adult
Endocrinology
Ras gene family
Cytology
Gene expression
medicine
Biomarkers, Tumor
Humans
Gene Regulatory Networks
Genetic Predisposition to Disease
Thyroid Neoplasms
Thyroid Nodule
Aged
Retrospective Studies
Gene Expression Profiling
Thyroid Cancer and Nodules
Middle Aged
medicine.disease
Genes, ras
Phenotype
RAS Mutation
Mutation
Female
Indeterminate
Transcriptome
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Thyroid
- Accession number :
- edsair.doi.dedup.....7c3b81345f3d7f636307a5c484390b8d