Center of Excellence in Genomic Medicine Research, Department of Medical Laboratory Technology, Faculty of Applied Medical Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
Department of Biochemistry, Faculty of Sciences, King Abdulaziz University, Jeddah, Saudi Arabia.
PLoS One. 2020 Jun 30;15(6):e0234566. doi: 10.1371/journal.pone.0234566. eCollection 2020.
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.
桥本甲状腺炎（HT）存在于约 30%的甲状腺乳头状癌（PTC）中。这种自身免疫性疾病的遗传易感性尚不完全清楚。我们分析了 13 例 HT、8 例合并 HT 的 PTC、6 例不合并 HT 的 PTC、6 例微小 PTC（mPTC）和 3 例正常甲状腺（TN）样本的微阵列表达谱。基于 FDR 调整后的 p 值≤0.05 和倍数变化（FC）>2，定义了 4 个比较组，分别为 HT 与 TN；PTC 伴 HT 与 TN；PTC 不伴 HT 与 TN；mPTC 与 TN。Venn 图显示了 15 个不同的相交和不相交的差异表达基因（DEG）集，其中一组 71 个 DEG，存在于 HT 与 TN 的比较组 HT 与 PTC 伴 HT 的比较组中，包含与免疫和炎症功能相关的基因、氧化应激和活性氧（ROS）、DNA 损伤和 DNA 修复、细胞周期和细胞凋亡的相对数量最多；大多数 71 个 DEG 上调，上调最明显的 DEG 包括许多免疫球蛋白 κ 可变基因和其他免疫相关基因，如 CD86 分子（CD86）、白细胞介素 2 受体γ（IL2RG）和干扰素、α 诱导蛋白 6（IFI6）。上调基因优先与其他基因本体（GO）相关，如 STAT1、MMP9、TOP2A 和 BRCA2。生物功能分析揭示了与免疫原性功能相关的途径。进一步的数据分析集中在来自 HT 与 TN 比较组的非相交 358 个 DEG 集，以及来自所有 4 个比较组交集的 950 个 DEG 集。总之，这项研究表明，除了与免疫/炎症相关的基因外，与氧化应激、ROS、DNA 损伤、DNA 修复、细胞周期和细胞凋亡相关的基因在 HT 和 PTC 伴 HT 的数据集之间也存在类似的失调。这些发现与慢性炎症反应伴随着与致癌转化相关的基因和生物功能失调的遗传序列概念一致。生成的数据集可作为识别候选基因和生物标志物的来源，这些基因和生物标志物可实际用于临床应用。
