👤 Mathilde Munier

Aqueous humor (AH) can be easily and safely used to evaluate disease-specific biomarkers in ocular disease. The aim of this study was to identify specific proteins biomarkers in the AH of retinoblastoma (RB) patients at various stages of the disease. We analyzed the proteome of 53 AH samples using high-resolution mass spectrometry. We grouped the samples according to active vitreous seeding (Group 1), active aqueous seeding (Group 2), naive RB (group 3), inactive RB (group 4), and congenital cataracts as the control (Group 5). We found a total of 889 proteins in all samples. Comparative parametric analyses among the different groups revealed three additional proteins expressed in the RB groups that were not expressed in the control group. These were histone H2B type 2-E (HISTH2B2E), InaD-like protein (PATJ), and ubiquitin conjugating enzyme E2 V1 (UBE2V1). Upon processing the data of our study with the OpenTarget Tool software, we found that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) and CD44 were more highly expressed in the RB groups. Our results provide a proteome database regarding AH related to RB disease that may be used as a source of biomarkers. Further prospective studies should validate our finding in a large cohort of RB patients. Show less

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