ECE2024 Eposter Presentations Pituitary and Neuroendocrinology (214 abstracts)
Vasopressin and androgen receptors as potential therapeutic targets in corticotroph pitnets
Maria Francesca Birtolo 1,2 , Antoan Stefan Sojat 3 , Bertrand Baussart 1,4 , Camille Sollier 5 , Nesrine Benanteur 1 , Xavier Bertagna 5 , Anne Jouinot 1,5 , Jerome Bertherat 1,5 , Guillaume Assié 1,5 & Chiara Villa 1,6
1INSERM U1016, Université Paris Cité, CNRS, Inserm, Institut Cochin, Genomics and signaling of endocrine tumors, Paris, France;2Humanitas University, Department of Biomedical Sciences, Pieve Emanuele (MI), Italy;3University Clinical Centre of Serbia, National Centre for Infertility and Endocrinology of Gender, Clinic for Endocrinology Diabetes and Metabolic Diseases, Belgrade, Serbia;4Hôpital Universitaire Pitié-Salpêtrière, APHP, Sorbonne Université, Department of Neurosurgery, Paris, France;5Métabolisme Et Cancer, CHU Cochin, APHP, Université Paris Cité, Département Endocrinologie, Paris, France;6Hôpital Universitaire Pitié-Salpêtrière, APHP, Sorbonne Université, Department of Neuropathology, Paris, France
Corticotroph Pituitary Neuroendocrine Tumours (Co-PitNETs) show significant differences in cortisol secretion, responses to existing therapies and gene expression andstill pose a challenge for patient management.
Aim: to explore possible novel therapeutic targets in Co-PitNETs (functioning and silent) through transcriptome analysis (RNA sequencing) and immunohistochemistry.
Methods: Transcriptomic data from a previously reported dataset of 134 PitNETs (T-cohort) (Neou M, Cancer Cell. 2020) were used to select potential therapeutic targets that were overexpressed in Co-PitNETs in comparison to other PitNETs types. Among the overexpressed genes, AVPR1B, encoding the Vasopressin V1b receptor, and AR, encoding the androgen receptor (AR) were validated in two cohorts including all PitNETs types (VI-cohort = 94 PitNETs and ARI-cohort = 66 PitNETs) by immunohistochemical analysis.
Results: In the T-cohort, AVPR1B gene was the most differentially overexpressed gene in each transcriptomic group of Co-PitNETs, independent of their clinical presentation (functionning vs silent) and the USP8 status (Kruskal-Wallis, P<10-14). Focusing on hormone receptors, AR gene was significantly overexpressed in corticotroph groups when compared to other PitNETs types. The immunohistochemical analysis of the VI-cohort confirmed higher AVPR1B immunostaining in Co-PitNETs than in other PitNET types (Kruskal-Wallis, P<10-6). Silent Co-PitNETs largely expressed AVPR1B (median 70%), more than functioning Co-PitNETs (median 20%, Wilcoxon P= 0.04). In the ARI-cohort, AR was more expressed in Co-PitNETs, mostly in functioning ones (Wilcoxon, P=0.04), and significantly more than in other PitNET types (Kruskal-Wallis, P<10-6).
Conclusion: AVPR1B and AR are overexpressed in Co-PitNETs representing a possible novel targets for future medical treatments.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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