Differential proteomic expression in non-functional pituitary neuroendocrine tumours and pituitary glands

Pituitary neuroendocrine tumours (PitNETs) are common accounting for 10 to 25 % of all intracranial tumours. This project describes the feasibility of developing a novel membrane-based biomarker that could be used for fluorescent guided surgery. The aim was to catalogue the differential expression of membrane proteins between non-functional PitNETs and pituitary glands.

Ten pituitary gland tissue specimens were obtained from the National Institute of Health (NIH) NeuroBio-Bank and twenty non-functional PitNETs were obtained from the Northwestern University Nervous System Tumour Bank. Mass spectrometry analysis using an Orbitrap Fusion Lumos Tribrid Mass Spectrometer linked to a Dionex Ultimate 3000 UPLC system was undertaken. Data Dependent Acquisition Mass Spectrometry and Data Independent Acquisition Mass Spectrometry was then completed. Pathway enrichment analysis was performed using clusterProfiler v4.6.0. Functional enrichment analysis was conducted using Gene Ontology terms and Reactome pathways.

Differential expression analysis between the two groups revealed a total of 2110 significant differently expressed proteins (DEPs), with 1387 of these also having a Log2 fold change either greater than 1, or less than -1. Of the 2110 DEPs, 925 were upregulated in tumours compared to control, while 1185 were downregulated.

We have demonstrated a proteomic comparison between non-functional PitNETs and normal pituitary glands. These results demonstrate differences consistent with contemporary literature but shows that NOTCH3 and PTPRJ are up-regulated in non-functional PitNETs compared to pituitary glands.