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Series GSE126698 Query DataSets for GSE126698
Status Public on Jul 07, 2020
Title IGF2BP1 is the first positive marker for anaplastic thyroid carcinoma diagnosis [RNA-Seq]
Organism Homo sapiens
Experiment type Expression profiling by high throughput sequencing
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 Total RNA-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 18, 2019
Last update date Aug 08, 2020
Contact name Danny Misiak
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)
GPL15456 Illumina HiScanSQ (Homo sapiens)
Samples (28)
GSM3611484 A3 [RNA-Seq]
GSM3611485 A4 [RNA-Seq]
GSM3611486 A5 [RNA-Seq]
This SubSeries is part of SuperSeries:
GSE126729 IGF2BP1 is the first positive marker for anaplastic thyroid carcinoma diagnosis
BioProject PRJNA523137
SRA SRP186236

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

Supplementary file Size Download File type/resource
GSE126698_DE_Thyroid_totalRNA_ATC_others_all.csv.gz 5.2 Mb (ftp)(http) CSV
GSE126698_DE_Thyroid_totalRNA_all.csv.gz 8.0 Mb (ftp)(http) CSV
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Raw data are available in SRA
Processed data are available on Series record

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