Abstract
Hashimoto's thyroiditis (HT) is present in the background of around 30% of papillary thyroid carcinomas (PTCs). The genetic predisposition effect of this autoimmune condition is not thoroughly understood. We analyzed the microarray expression profiles of 13 HT, eight PTCs with (w/) coexisting HT, six PTCs without (w/o) coexisting HT, six micro PTCs (mPTCs), and three normal thyroid (TN) samples. Based on a false discovery rate (FDR)-adjusted p-value ≤ 0.05 and a fold change (FC) > 2, four comparison groups were defined, which were HT vs. TN; PTC w/ HT vs. TN; PTC w/o HT vs. TN; and mPTC vs. TN. A Venn diagram displayed 15 different intersecting and non-intersecting differentially expressed gene (DEG) sets, of which a set of 71 DEGs, shared between the two comparison groups HT vs. TN ∩ PTC w/ HT vs. TN, harbored the relatively largest number of genes related to immune and inflammatory functions; oxidative stress and reactive oxygen species (ROS); DNA damage and DNA repair; cell cycle; and apoptosis. The majority of the 71 DEGs were upregulated and the most upregulated DEGs included a number of immunoglobulin kappa variable genes, and other immune-related genes, e.g., CD86 molecule (CD86), interleukin 2 receptor gamma (IL2RG), and interferon, alpha-inducible protein 6 (IFI6). Upregulated genes preferentially associated with other gene ontologies (GO) were, e.g., STAT1, MMP9, TOP2A, and BRCA2. Biofunctional analysis revealed pathways related to immunogenic functions. Further data analysis focused on the set of non-intersecting 358 DEGs derived from the comparison group of HT vs. TN, and on the set of 950 DEGs from the intersection of all four comparison groups. In conclusion, this study indicates that, besides immune/inflammation-related genes, also genes associated with oxidative stress, ROS, DNA damage, DNA repair, cell cycle, and apoptosis are comparably more deregulated in a data set shared between HT and PTC w/ HT. These findings are compatible with the conception of a genetic sequence where chronic inflammatory response is accompanied by deregulation of genes and biofunctions associated with oncogenic transformation. The generated data set may serve as a source for identifying candidate genes and biomarkers that are practical for clinical application.
Highlights
Hashimoto’s thyroiditis (HT), known as chronic lymphocytic thyroiditis, is induced by an autoimmune response where immune cells produce autoantibodies that target thyroid antigens, in first instance thyroid peroxidase (TPO) and thyroglobulin (TG) leading to atrophy and transformation of thyroid cells [1, 2]
We focused in first inTstance on the 71 differentially expressed gene (DEG), which were shared between the two comparison groups HT vs. TN papillary thyroid carcinomas (PTCs) w/ HT vs. TN
We focused on the nonshared 358 DEGs derived from the comparison group HT vs. TNTand on the 950 DEGTs, which are shared betwTeen the four comparison groups, i.e., HT vs. TN PTC w/ HT vs. TN PTC w/o HT vs. TN micro PTCs (mPTCs) vs. TN
Summary
Hashimoto’s thyroiditis (HT), known as chronic lymphocytic thyroiditis, is induced by an autoimmune response where immune cells produce autoantibodies that target thyroid antigens, in first instance thyroid peroxidase (TPO) and thyroglobulin (TG) leading to atrophy and transformation of thyroid cells [1, 2]. This autoimmune reaction is caused by infiltrating autoreactive T lymphocytes and other components of the immune defense system that constitute an inflammatory infiltrate, which under chronic conditions leads to thyroiditis and hypothyroidism [2, 3]. Several studies including a meta-analysis on fine-needle aspiration (FNA) and thyroidectomy studies reported HT as a risk factor for papillary thyroid carcinoma (PTC) development, and this observation was mainly based on the proportionally higher incidence of PTC with (w/) HT compared to PTC without (w/o) HT [9, 10]
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