Valentine Suteau1,2, Valérie Seegers3, Mathilde Munier1,2,4, Rym Ben Boubaker2, Cécile Reyes5, David Gentien5, Méline Wery6, Anne Croué7, Frédéric Illouz1,4,8, Antoine Hamy9, Patrice Rodien1,2,4,8, Claire Briet1,2,4,8. 1. Département d'Endocrinologie-diabétologie nutrition, CHU Angers, Angers, France. 2. Faculty of Health, University of Angers (CHU Angers), Inserm 1083, CNRS 6015, MITOVASC, SFR ICAT, Angers, France. 3. Institut de Cancérologie de l'Ouest, Service de Biométrie, Angers, France. 4. Centre de référence des maladies rares de la Thyroïde et des Récepteurs Hormonaux, Endo-ERN centre for rare endocrine diseases, Angers, France. 5. Institut Curie, Plateforme Génomique, Paris, France. 6. Faculty of Health, University of Angers (CHU Angers), SFR ICAT, Angers, France. 7. Département de Pathologie Cellulaire et Tissulaire, CHU Angers, Angers, France. 8. Centre de compétence TUTHYREF, TUTHYREF Network, Angers, France. 9. Service de chirurgie viscérale, CHU d'Angers, Angers, France.
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.
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.