Comparison of gene expression data of hot and cold thyroid nodules and TSH stimulated primary thyroid cell cultures

Abstract

Our gene expression analysis of autonomously functioning thyroid nodules (AFTNs) and cold thyroid nodules (CTNs) each in comparison to their surrounding tissues led to the identification of an inactive TGF-β signaling in AFTNs and of increased expression of cell cycle associated genes and indications for a relevance of Gq-PKC signaling in CTNs. Both, AFTNs and CTNs are characterized by an increased proliferation, however they are contrary in their functional activity. Therefore, with the aim to further specify specific findings for each entity and to discover common mechanisms like those leading to increased proliferation in both, AFTNs and CTNs, we now compared gene expression of AFTNs, CTNs and TSH stimulated primary thyroid epithelial cell cultures with each other. Since combinations of co-regulated genes are more likely to reveal molecular disease mechanisms we now used a modified procedure which groups co-regulated genes within one “gene set“. Thereby, we identified gene sets with concordant expression patterns in AFTNs and CTNs or sets of co-regulated genes which are either specific for AFTNs or for CTNs. Interestingly, we found one positively co-regulated gene set in the AFTNs, that showed no regulation in the CTNs, whereas these genes are also positively co-regulated in TSH stimulated primary cell cultures. In addition to TPO and SIAT1 this set of co-regulated genes comprises several metallothioneins. Despite their role in the thyroid is unknown so far, their appearance in one group with TPO and SIAT1 indicates a relevance of these genes for the regulation of the increased function of AFTNs. Moreover, co-regulated genes with a decreased expression in AFTNs are characterized by co-regulation and a decreased expression in CTNs. However, these expression patterns for genes with decreased expression are not of relevance in the cell cultures. These findings suggest, that TSH stimulated primary cell cultures can be used as a model of increased thyroid function (AFTNs), whereas they are not a suitable model for increased proliferation in AFTNs or CTNs.