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J Neurol Surg B Skull Base 2024; 85(04): 340-346
DOI: 10.1055/a-2088-6594
Original Article

Transcriptome-Derived Ligand-Receptor Interactome of Major PitNET Subgroups

Sai Batchu
1   Cooper Medical School, Rowan University, Camden, New Jersey, United States
,
Michael Joseph Diaz
2   College of Medicine, University of Florida, Gainesville, Florida, United States
,
Aashay Patel
2   College of Medicine, University of Florida, Gainesville, Florida, United States
,
Akshay Reddy
2   College of Medicine, University of Florida, Gainesville, Florida, United States
,
Brandon Lucke-Wold 
3   Department of Neurosurgery, University of Florida, Gainesville, Florida, United States
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Abstract

Introduction Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors which can impart significant disability owing to their locally invasive potential. To date, the gamut of PitNET subtypes remains ill-understood at the ligand-receptor (LR) interactome level, potentially limiting therapeutic options. Here, we present findings from in silico analysis of LR complexes formed by PitNETs with clinical presentations of acromegaly, Cushing's disease, high prolactin production, and without symptoms of hormone hypersecretion.

Methods Previously published PitNET gene expression data was acquired from ArrayExpress. These data represented all secretion types. LR interactions were analyzed via a crosstalk score approach.

Results Cortisol (CORT) ligand was significantly involved in tumor-to-tumor signaling across all PitNET subtypes but prolactinomas, which evidenced active CORT depletion. Likewise, CCL25 ligand was implicated in 20% of the top LR complex interactions along the tumor-to-stroma signaling axis, but silent PitNETs reported unique depletion of the CCL25 ligand. Along the stroma-to-tumor signaling axis, all clinical PitNET subtypes enriched stromal vasoactive intestinal polypeptide ligand interactions with tumor secretin receptor. All clinical PitNET subtypes enriched stromal DEFB103B (human β-defensin 103B) ligand interactions with stromal chemokine receptors along the stroma-to-stroma signaling axis. In PitNETs causing Cushing's disease, immune checkpoint ligand CD274 reported high stromal expression, and prolactinomas reported low stromal expression. Moreover, prolactinomas evidenced distinctly high stromal expression of immune-exhausted T cell response marker IL10RA compared with other clinical subtypes.

Conclusion Relative crosstalk score analysis revealed a great diversity of LR complex interactions across clinical PitNET subtypes and between solid tumor compartments. More data are needed to validate these findings and exact clinical importance.

Keywords

PitNET - clinical subtype - Cushing's disease - acromegaly - ligand-receptor interactions - relative crosstalk score


Publication History

Received: 11 December 2022

Accepted: 03 May 2023

Accepted Manuscript online:
08 May 2023

Article published online:
12 June 2023

© 2023. Thieme. All rights reserved.

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 

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