SFEBES2022 Oral Poster Presentations Reproductive and Neuroendocrinology (4 abstracts)
Identification of differentially activated pathways in recurrent non-functioning pituitary tumours using quantitative proteomics and bioinformatics analysis
Ashutosh Rai 1,2 , Soujanya D Yelamanchi 3 , Sayka Barry 1 , Bishan D Radotra 4 , Sunil K Gupta 5 , Rajesh Chhabra 5 , Akhilesh Pandey 6,4 , Márta Korbonits 1 & Pinaki Dutta 2
1Centre for Endocrinology, William Harvey Research Institute, Queen Mary University of London, London, United Kingdom; 2Department of Endocrinology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 3Molecular Biophysics Unit, Indian Institute of Science, Bangalore, India; 4Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 5Department of Neurosurgery, Postgraduate Institute of Medical Education and Research, Chandigarh, India; 6Institute of Bioinformatics, Bangalore, India; 7Institute of Genetic Medicine, and the Division of Proteomics, Mayo Clinic, Minnesota, United state of America
Background: No predictive biomarkers have been identified for clinically nonfunctioning pituitary tumour (NFPT) recurrence, with Ki67 being controversial. We employed quantitative mass spectrometry-based analyses to examine the differential expression of proteins in NFPTs.
Methods: NFPTs were sub-grouped: non-invasive/non-recurrent group (NI/NR-G, n=5), invasive group (I-G, n=10) and recurrent group (R-G, n=5). Invasiveness was determined Knosp classification 3,4; histopathological invasion (bone/dura/mucosa) and intraoperative findings. Mean follow-up was 17.4 (
Results: Out of 5903 identified proteins, 441 were differentially expressed in I-G (339 overexpressed, 102 underexpressed) and 683 in R-G (628 overexpressed, 55 underexpressed). In invasive tumours, IL-8 signalling (DEFA1, GNAI3, ITGAM, ITGB3, MPO) (-log p-value, Z-score:1.4,2.2) and RGS12, a regulator of GPCR signalling, with its 13 downstream members were enriched (9.0E-07,2.5). Recurrent tumours had significantly activated actin cytoskeleton (6.8,3.0) and Integrin-linked kinase (ILK) signalling (5.6,3.0). GATA1 was activated in R-G (2.5E-12,2.2) together with overexpression of further 24 downstream proteins involving actin cytoskeleton and ILK signalling. Members of the interleukin pathway were overexpressed in R-G (IL17RA receptor (1.28E-12,5.5) as well as IL6, IL6R, IL4, IL17A, IL1B, IL22, IL1A, IL23A and IL1. IL6 is most significantly upregulated protein (Z-score,4.6). Cytoskeleton pathway member PRDM1, a transcription factor, was upregulated in both I-G and R-G.
Conclusions: This study provides in-depth proteomics analysis of NFPTs. Actin cytoskeleton was upregulated in both I-G and R-G, with stronger effect in R-G, while ILK signalling, especially IL6, showed specifically high levels in recurrent NFPTs.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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