Study on molecular diagnostic markers of differentiated thyroid tumors
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Abstract:
Objective:To identify molecular markers for accurate diagnosis of thyroid cancer the molecular phenotypes of varied proteiumark were evaluated in differentiated thyroid cancer (DTC) and benign thyroid lesions. Methods:Tissue microarrays containing 100 benign and 99 malignant thyroid lesions were stained for a panel of 57 molecular markers. Correlation between the marker staining and tumor pathology (DTC versus benign tumor) were determined using contingency table and Mann-Whitney U (MU) tests. A Random Forests classifier algorithm was also utilized to identify meaningful important molecular classifiers. Results: Of the 57 diagnostic markers evaluated, 35 (61%) were significantly associated with a DTC diagnosis after multiple testing correction. Among them, 8 markers were downregulated and 27 ones upregulated in DTC, when compared with benign thyroid tumor. The most significant markers for DTC diagnosis were Galectin-3, Cytokeratin 19, Vascular Endothelial Growth Factor, Androgen Receptor, p16, Aurora-A, and HBME-1. Using the entire molecular marker panel, a Random Forests algorithm was able to classify a neoplasm as DTC or benign tumor with an estimated sensitivity of 87.9%, specificity of 94.0%, and accuracy of 91.0%. Conclusion:Evaluating the DTC and benign thyroid tumor molecular phenotypes has allowed us to identify a diagnostic marker panel, which may help differentiate DTC with benign tumors and improve patient selection for thyroid surgery.