Background
Currently, anaplastic thyroid carcinoma has a very poor prognosis and there is an
unmet need for new therapeutic options. Therefore, this study aims to identify upregulated
genes in anaplastic thyroid carcinoma with known drug interactions that could serve
as new therapeutic targets.
Methods
Publicly available microarray expression profiles of anaplastic thyroid carcinoma
and normal thyroid tissue were collected. FGmRNA-profiling was applied, which is a
recently developed method that enhances the ability to capture the downstream effects
of genomic alterations on gene expression levels. Next, a comparison between FGmRNA-profiles
of anaplastic thyroid carcinoma and normal thyroid samples was performed. Significantly
upregulated genes in ATC were prioritized based on: 1) known interaction with antineoplastic
drugs, 2) current drug development status in human, and 3) association with biologic
pathways known to be involved in anaplastic thyroid carcinoma carcinogenesis.
Results
In the study, 25 anaplastic thyroid carcinoma and 80 normal thyroid samples were included
for FGmRNA-profiling. Class comparison identified 301 significantly upregulated genes.
Following prioritization, MTOR, MET, WEE1, PSMD1, MERTK, FGFR3, RARG, and ESR2 were
identified as potential therapeutic targets.
Conclusion
We prioritized 8 potential therapeutic druggable targets in anaplastic thyroid carcinoma.
Ultimately, inhibition of these therapeutic targets might improve patient outcome
in anaplastic thyroid carcinoma by reducing locoregional disease and distant metastases.
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Article info
Publication history
Published online: November 16, 2016
Accepted:
June 18,
2016
Footnotes
Supported by the Bas Mulder award of Alpe d’HuZes/Dutch Cancer Society (RUG 2013–5960) and a Mandema Stipendium to R.S.N. Fehrmann.
Identification
Copyright
© 2016 Elsevier Inc. All rights reserved.
