Nodular goiter and hyperplastic lesion of the thyroid share common deregulated expression profiles

Abstract

BackgroundProliferative thyroid lesions including nodular goiter andhyperplastic lesion are very common in the Middle Eastand North African (MENA) region [1]. Hyperplasticlesions are also regarded as a subcategory of goiter.High-density expression profiles in these benign thyroidlesionsarenotsurveyedindetail[2].Inanefforttoestablish gene expression profiles that distinguish bothlesions from each other and from normal thyroid (TN)tissue, we employed state-of-the-art oligonucleotidemicroarray technology.Materials and methodsWhole transcript expression profiles were generated in17 goiters, 14 hyperplastic lesions and 7 TN samples uti-lizing Affymetrix HuGene 1.0 ST arrays. We used thedefault analysis method for generating a threshold of sig-nificance for differential expression (p-value with a falsediscovery rate≤ 0.05 and a fold change > 2). PartekGenomics Suite and Ingenuity Pathway Analysis softwarepackages were utilized to interpret data sets.ResultsExpression profiles of goiters and hyperplastic lesionswere highly related and no transcripts were differentiallyexpressed between these two thyroid lesions under thegiven statistical threshold values. However, more than10000 genes were differentially expressed between goi-ters, as well as hyperplastic lesions, and TN samples. Themost differentially expressed transcripts were in factdownregulated in both thyroid lesions in comparison toTN samples and include geneslike olfactory receptor,family 6, subfamily N (OR6N2), glial cells missing homo-log 1, Drosophila (GCM1), family with sequence similar-ity 138, member B (FAM138B), prostate-specific P704PmRNA (P704P), and olfactory receptor, family 5, subfam-ily H, member 14 (OR5H14). The most upregulated tran-scripts in goiters and hyperplastic lesions vs TN samplesinclude genes as cytochrome c oxidase assembly proteinCOX15 homolog (COX15), dyskeratosis congenita 1,dyskerin (DKC1), and DnaJ (Hsp40) homolog, subfamilyA, member 2 (DNAJA2). Networks which were mostderegulated in goiter and hyperplastic lesion in compari-son to TN tissue share similar functions although certainpathways seem to be differentially affected in both thyr-oid lesions.ConclusionsOur study indicates that goiter and hyperplastic lesionshare common deregulated expression profiles in com-parison to TN tissue. As a certain number of goiters andhyperplastic lesions bear the capacity to develop to thyr-oid neoplasms, knowledge ofderegulated genes in theselesions may help to identify patients which are at elevatedrisk for developing thyroid carcinoma. Further studieshave to reveal which expression signatures in thesebenign thyroid lesions are in common with malignantcases.This study was supported by King Abdulaziz City forScience and Technology(KACST) grants 09-BIO707-03and 09-BIO820-03.