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Article Dans Une Revue Journal of Clinical Endocrinology and Metabolism Année : 2021

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

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Valentine Suteau
Valérie Seegers
  • Fonction : Auteur
Rym Ben Boubaker
  • Fonction : Auteur
Cécile Reyes
  • Fonction : Auteur
David Gentien
  • Fonction : Auteur
Méline Wery
  • Fonction : Auteur
Anne Croué
  • Fonction : Auteur
Frédéric Illouz
  • Fonction : Auteur
Antoine Hamy
  • Fonction : Auteur
Patrice Rodien
Claire Briet
  • Fonction : Auteur

Résumé

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.

Dates et versions

hal-03557034 , version 1 (04-02-2022)

Identifiants

Citer

Mathilde Munier, Valentine Suteau, Valérie Seegers, Rym Ben Boubaker, Cécile Reyes, et al.. G Protein–coupled Receptors in Radioiodine-refractory Thyroid Cancer in the Era of Precision Medicine. Journal of Clinical Endocrinology and Metabolism, 2021, 106 (8), pp.2221-2232. ⟨10.1210/clinem/dgab343⟩. ⟨hal-03557034⟩
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