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Series GSE126728 Query DataSets for GSE126728
Status Public on Jul 07, 2020
Title IGF2BP1 is the first positive marker for anaplastic thyroid carcinoma diagnosis [sWGS]
Organism Homo sapiens
Experiment type Other
Summary Anaplastic thyroid carcinomas (ATC) are rare, but represent the most lethal malignancy of the thyroid. Selective molecular markers and drivers distinguishing ATC from other thyroid carcinomas of follicular origin remain largely unknown, limiting advances in diagnosis and treatment. In a retrospective study, we analyzed gene expression in 36 ATC, 18 poorly-differentiated, 132 papillary and 55 follicular thyroid carcinoma, as well as 124 paired and un-paired normal thyroid tissues in three independent cohorts by RNA-sequencing and immunohistochemistry. RNA-sequencing data in the test cohort suggested selective ATC protein biomarkers. Evaluation of these revealed that ATCs are characterized by the de novo expression of various testis antigens, including melanoma-associated antigen A3 (MAGEA3), but most importantly the oncofetal IGF2 mRNA binding protein 1 (IGF2BP1). Shallow whole genome-sequencing essentially excluded, that IGF2BP1 upregulation results from gene copy number alterations. Immunohistochemical analyses in all three tumor cohorts confirmed selective de novo expression of IGF2BP1 protein in ATC. In sum, 75 % (27/36) of all tested ATC and 0.5 % (1/204) of poorly and well-differentiated thyroid carcinoma tissue samples were positive for IGF2BP1 protein. This indicates that IGF2BP1 protein expression identifies ATC with a diagnostic odds ratio of 612 (95 % CI: 74.6 to 5021). In addition, we found that MAGEA3 is exclusively, although less consistently upregulated in ATC, presenting with an odds ratio of 411 (95 % CI: 23.8 to 7098.7). Importantly, we provide confirmatory evidence that IGF2BP1 and MAGEA3 expression distinguishes ATC from partially differentiated thyroid carcinomas (PDTCs). IGF2BP1 furthermore identified ATC foci within low-grade follicular thyroid carcinoma. In conclusion, IGF2BP1 represents the most promising single-gene marker available for ATC, followed by MAGEA3, improving on current techniques. Robust markers are essential to help distinguish this high-grade malignancy from other thyroid carcinomas, to guide surgical decision making, therapy and post-resection/therapy monitoring strategies.
 
Overall design Shallow Whole Genome sequencing of ATC samples.
 
Contributor(s) Haase J, Misiak D, Pazaitis N, Bauer M, Braun J, Pötschke R, Mensch A, Bell JL, Dralle H, Siebolts U, Wickenhauser C, Lorenz K, Hüttelmaier S
Citation(s) 32719445
Submission date Feb 19, 2019
Last update date Jul 30, 2020
Contact name Danny Misiak
E-mail(s) danny.misiak@medizin.uni-halle.de
Phone +49345573962
Organization name Martin Luther University Halle-Wittenberg
Department Molecular Cell Biology
Lab Hüttelmaier Lab
Street address Kurt-Mothes-Str. 3a
City Halle (Saale)
ZIP/Postal code 06120
Country Germany
 
Platforms (1)
GPL24676 Illumina NovaSeq 6000 (Homo sapiens)
Samples (26)
GSM3611863 Sample 1 [WGS]
GSM3611864 Sample 2 [WGS]
GSM3611865 Sample 3 [WGS]
This SubSeries is part of SuperSeries:
GSE126729 IGF2BP1 is the first positive marker for anaplastic thyroid carcinoma diagnosis
Relations
BioProject PRJNA523135
SRA SRP186237

Download family Format
SOFT formatted family file(s) SOFTHelp
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Series Matrix File(s) TXTHelp

Supplementary file Size Download File type/resource
GSE126728_RAW.tar 170.0 Kb (http)(custom) TAR (of CSV)
SRA Run SelectorHelp
Raw data are available in SRA
Processed data provided as supplementary file

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