Expression of Sodium-Iodide Symporter Depending on Mutational Status and Lymphocytic Thyroiditis in Papillary Thyroid Carcinoma
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Background and Objectives: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). Materials and Methods: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. Results: The PTCs with the BRAFV600E mutation and the coexistence of BRAFV600E and TERT promoter mutations showed significantly lower expression of NIS (p＜0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p＜0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p＜0.001) and negative correlations with expressions of genes involved in ERK signaling (r=−0.164, p＜0.001) and GLUT-1 gene (r=−0.204, p＜0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. Conclusion: The NIS expression was reduced by the BRAFV600E mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.
Abstract
Background and Objectives: Sodium-iodine symporter (NIS) is a marker for the degree of differentiation in thyroid cancer. The genetic factors or microenvironment surrounding tumors can affect transcription of NIS. In this study, we investigated the NIS mRNA expression according to mutational status and coexistent lymphocytic thyroiditis in papillary thyroid cancer (PTC). Materials and Methods: The RNA expression levels of NIS in the samples from database of The Caner Genome Atlas (TCGA; n=494) and our institute (n=125) were analyzed. Results: The PTCs with the BRAFV600E mutation and the coexistence of BRAFV600E and TERT promoter mutations showed significantly lower expression of NIS (p＜0.001, respectively), and those with BRAF-like molecular subtype also had reduced expression of NIS (p＜0.001). NIS expression showed a positive correlation with thyroid differentiation score (r=0.593, p＜0.001) and negative correlations with expressions of genes involved in ERK signaling (r=−0.164, p＜0.001) and GLUT-1 gene (r=−0.204, p＜0.001). The PTCs with lymphocytic thyroiditis showed significantly higher NIS expression (p=0.013), regardless of mutational status. Conclusion: The NIS expression was reduced by the BRAFV600E mutation and MAPK/ERK pathway activation, but restored by the presence of lymphocytic thyroiditis.
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