G Protein-coupled Receptors in Radioiodine-refractory Thyroid Cancer in the Era of Precision Medicine.

Abstract

CONTEXT:

Radioiodine-refractory thyroid cancers have poor outcomes and limited therapeutic options (tyrosine kinase inhibitors) due to transient efficacy and toxicity of treatments. Therefore, combinatorial treatments with new therapeutic approaches are needed. Many studies link G protein-coupled receptors (GPCRs) to cancer cell biology.

OBJECTIVE:

To perform a specific atlas of GPCR expression in progressive and refractory thyroid cancer to identify potential targets among GPCRs aiming at drug repositioning.

METHODS:

We analyzed samples from tumor and normal thyroid tissues from 17 patients with refractory thyroid cancer (12 papillary thyroid cancers [PTCs] and 5 follicular thyroid cancers [FTCs]). We assessed GPCR mRNA expression using NanoString technology with a custom panel of 371 GPCRs. The data were compared with public repositories and pharmacological databases to identify eligible drugs. The analysis of prognostic value of genes was also performed with TCGA datasets.

RESULTS:

With our transcriptomic analysis, 4 receptors were found to be downregulated in FTC (VIPR1, ADGRL2/LPHN2, ADGRA3, and ADGRV1). In PTC, 24 receptors were deregulated, 7 of which were also identified by bioinformatics analyses of publicly available datasets on primary thyroid cancers (VIPR1, ADORA1, GPRC5B, P2RY8, GABBR2, CYSLTR2, and LPAR5). Among all the differentially expressed genes, 22 GPCRs are the target of approved drugs and some GPCRs are also associated with prognostic factors.

DISCUSSION:

For the first time, we performed GPCR mRNA expression profiling in progressive and refractory thyroid cancers. These findings provide an opportunity to identify potential therapeutic targets for drug repositioning and precision medicine in radioiodine-refractory thyroid cancer.

• Authors: Valentine Suteau, Valérie Seegers, Mathilde Munier, Rym Ben Boubaker, Cécile Reyes, David Gentien, Méline Wery, Anne Croué, Frédéric Illouz, Antoine Hamy, Patrice Rodien, Claire Briet
• Journal: The Journal of clinical endocrinology and metabolism (J Clin Endocrinol Metab) Vol. 106 Issue 8 Pg. 2221-2232 (07 13 2021) ISSN: 1945-7197 [Electronic] United States
• PMID: 34000025 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

Chemical References

• Receptors, G-Protein-Coupled

Topics

• Adenocarcinoma, Follicular (genetics, metabolism, pathology)
• Adult
• Aged
• Female
• Gene Expression Profiling
• Humans
• Male
• Middle Aged
• Precision Medicine
• Receptors, G-Protein-Coupled (genetics, metabolism)
• Retrospective Studies
• Thyroid Cancer, Papillary (genetics, metabolism, pathology)
• Thyroid Gland (metabolism, pathology)
• Thyroid Neoplasms (genetics, metabolism)