Document Details
Document Type |
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Article In Journal |
Document Title |
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Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid Comparison of microarray expression profiles between follicular variant of papillary thyroid carcinomas and follicular adenomas of the thyroid |
Document Language |
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English |
Abstract |
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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 a p-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 a BRAF mutation, revealed 55
transcripts that were significantly differentially expressed, 40 of which were upregulated and 15 downregulated in
FVPTCs vs. FAs. Amongst the most significantly upregulated genes in FVPTCs were GABA B receptor, 2 (GABBR2),
neuronal cell adhesion molecule (NRCAM), extracellular matrix protein 1 (ECM1), heparan sulfate 6-O-sulfotransferase 2
(HS6ST2), and retinoid X receptor, gamma (RXRG). The most significantly downregulated genes in FVPTCs included
interaction protein for cytohesin exchange factors 1 (IPCEF1), G protein-coupled receptor 155 (GPR155), Purkinje cell
protein 4 (PCP4), chondroitin sulfate N-acetylgalactosaminyltransferase 1 (CSGALNACT1), and glutamate 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. |
ISSN |
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1471-2164 |
Journal Name |
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BMC genomics |
Volume |
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16 |
Issue Number |
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1 |
Publishing Year |
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1437 AH
2016 AD |
Article Type |
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Article |
Added Date |
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Wednesday, October 5, 2016 |
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Researchers
Hans-Juergen Schulten | Schulten, Hans-Juergen | Investigator | Doctorate | hschulten@kau.edu.sa |
Ibtisam Baghallab | Baghallab, Ibtisam | Researcher | Master | |
Nadia Bagatian | Bagatian, Nadia | Researcher | Master | |
Ohoud Subhi | Subhi, Ohoud | Researcher | | |
Sajjad Karim | Karim, Sajjad | Researcher | Doctorate | |
Mohammad Al-Qahtani | Al-Qahtani, Mohammad | Researcher | Doctorate | |
Zuhoor Al-Mansouri | Al-Mansouri, Zuhoor | Researcher | | |
Hosam Al-Aradati | Al-Aradati, Hosam | Researcher | | |
Abdulmonem Al-Mutawa | Al-Mutawa, Abdulmonem | Researcher | | |
Jaudah Al-Maghrabi | Al-Maghrabi, Jaudah | Researcher | Doctorate | |
Adel Johary | Johary, Adel | Researcher | | |
Abdulrahman Meccawy | Meccawy, Abdulrahman | Researcher | | |
Khalid Al-Ghamdi | Al-Ghamdi, Khalid | Researcher | | |
Osman Al-Hamour | Al-Hamour, Osman | Researcher | | |
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