Open AccessGenetic relationship between Hashimoto`s thyroiditis and papillary thyroid carcinoma with coexisting Hashimoto`s thyroiditis
Author(s) -
Ohoud Subhi,
Hans-Juergen Schulten,
Nadia Bagatian,
Roa'a Al-Dayini,
Sajjad Karim,
Sherin Bakhashab,
Reem Alotibi,
Alaa Alahmadi,
Manar Ata,
Aisha Elaimi,
Saad M. Almuhayawi,
Majdi Mansouri,
Khalid A. AlGhamdi,
Osman A Hamour,
Awatif Jamal,
Jaudah Al-Maghrabi,
Mohammed AlQahtani
Publication year - 2020
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0234566
Subject(s) - thyroiditis , thyroid carcinoma , medicine , thyroid cancer , endocrinology , immune system , thyroid , biology , cancer research , microbiology and biotechnology , immunology
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.