Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid. (December 2015)

• Record Type: Journal Article
• Authors: Schulten, Hans-Juergen; Al-Mansouri, Zuhoor; Baghallab, Ibtisam; Bagatian, Nadia; Subhi, Ohoud; Karim, Sajjad; Al-Aradati, Hosam; Al-Mutawa, Abdulmonem; Johary, Adel; Meccawy, Abdulrahman; Al-Ghamdi, Khalid; Al-Hamour, Osman; Al-Qahtani, Mohammad; Al-Maghrabi, Jaudah
• Is Part Of: BMC genomics. Volume 16:Number 1(2015)
• Page Start: 1
• Page End: 11
• Publication Date: 2015-12
• Subjects: whole-transcript oligonucleotide microarrays; expression profiling -- follicular variant of papillary thyroid carcinoma (FVPTC) -- follicular adenoma (FA) of the thyroid.; Genomes -- Periodicals; Gene mapping -- Periodicals; Genomics -- Periodicals; Base Sequence -- Periodicals; Chromosome Mapping -- Periodicals; Genetic Techniques -- Periodicals; Sequence Analysis, DNA -- Periodicals; 572.8605
• DOI: 10.1186/1471-2164-16-S1-S7
• Languages: English
• ISSNs: 1471-2164

Abstract

Abstract Background Follicular variant of papillary thyroid carcinoma (FVPTC) and follicular adenoma (FA) are histologically closely related tumors and differential diagnosis remains challenging. RNA expression profiling is an established method to unravel molecular mechanisms underlying the histopathology of diseases. Methods BRAF mutational status was established by direct sequencing the hotspot region of exon 15 in six FVPTCs and seven FAs. Whole-transcript arrays were employed to generate expression profiles in six FVPTCs, seven FAs and seven normal thyroid tissue samples. The threshold of significance for differential expression on the gene and exon level was ap -value with a false discovery rate (FDR) < 0.05 and a fold change cutoff > 2. Two dimensional average linkage hierarchical clustering was generated using differentially expressed genes. Network, pathway, and alternative splicing utilities were employed to interpret significance of expression data on the gene and exon level. Results Expression profiling in FVPTCs and FAs, all of which were negative for aBRAF mutation, revealed 55 transcripts that were significantly differentially expressed, 40 of which were upregulated and 15 downregulated in FVPTCsvs . FAs. Amongst the most significantly upregulated genes in FVPTCs wereGABA B receptor, 2 (GABBR2 ), neuronal cell adhesion molecule (NRCAM ), extracellular matrix protein 1 (ECM1 ), heparan sulfate 6-O-sulfotransferase 2 (HS6ST2 ), andretinoid X receptor, gamma (RXRG ). The most significantly downregulated genes in FVPTCs includedinteraction protein for cytohesin exchange factors 1 (IPCEF1 ), G protein-coupled receptor 155 (GPR155 ), Purkinje cell protein 4 (PCP4 ), chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1 ), andglutamate receptor interacting protein 1 (GRIP1 ). Alternative splicing analysis detected 87 genes, 52 of which were also included in the list of 55 differentially expressed genes. Network analysis demonstrated multiple interactions for a number of differentially expressed molecules including vitamin D (1, 25- dihydroxyvitamin D3) receptor (VDR), SMAD family member 9 (SMAD9), v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT), and RXRG. Conclusions This is one of the first studies using whole-transcript expression arrays to compare expression profiles between FVPTCs and FAs. A set of differentially expressed genes has been identified that contains valuable candidate genes to differentiate both histopathologically related tumor types on the molecular level.