Transcriptome-Derived Ligand-Receptor Interactome of Major PitNET Subgroups

Area of Science:

• Endocrinology
• Oncology
• Bioinformatics

Background:

• Pituitary neuroendocrine tumors (PitNETs) are rare skull base tumors with significant invasive potential.
• The ligand-receptor (LR) interactome of PitNET subtypes is poorly understood, limiting therapeutic strategies.
• This study investigates LR interactions across different PitNET clinical presentations.

Purpose of the Study:

• To analyze the LR interactome of PitNETs using in silico methods.
• To identify distinct signaling pathways in PitNET subtypes associated with acromegaly, Cushing's disease, prolactinoma, and non-functioning tumors.
• To explore tumor-to-tumor, tumor-to-stroma, and stroma-to-tumor signaling axes.

Main Methods:

• Acquisition of previously published PitNET gene expression data from ArrayExpress.
• Analysis of LR interactions using a crosstalk score approach.
• In silico modeling of ligand-receptor complexes.

Main Results:

• Cortisol (CORT) ligand was involved in tumor-to-tumor signaling across most PitNET subtypes, except prolactinomas which showed CORT depletion.
• CCL25 ligand was implicated in tumor-to-stroma signaling, with silent PitNETs showing CCL25 depletion.
• All PitNET subtypes showed stromal vasoactive intestinal polypeptide and DEFB103B ligand interactions.
• Cushing's disease PitNETs had high stromal CD274 expression, while prolactinomas had low expression and high IL10RA expression.

Conclusions:

• Ligand-receptor crosstalk analysis reveals significant diversity in PitNET subtypes and tumor compartments.
• Specific signaling pathways and ligand-receptor interactions differ across clinical presentations.
• Further research is needed to validate these findings and determine their clinical significance for PitNET treatment.