Rai, A and Yelamanchi, SD and Radotra, BD and Gupta, SK and Mukherjee, KK and Tripathi, M and Chhabra, R and Ahuja, CK and Kumar, N and Pandey, A and Korbonits, M and Dutta, P and Gaston-Massuet, C (2022) Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours. In: Acta Neuropathologica Communications, 10 (1).
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Abstract
Non-functioning pituitary tumours (NF-PitNETs) are common intracranial benign neoplasms that can exhibit aggressive behaviour by invading neighbouring structures and, in some cases, have multiple recurrences. Despite resulting in severe co-morbidities, no predictive biomarkers of recurrence have been identified for NF-PitNETs. In this study we have used high-throughput mass spectrometry-based analysis to examine the phosphorylation pattern of different subsets of NF-PitNETs. Based on histopathological, radiological, surgical and clinical features, we have grouped NF-PitNETs into non-invasive, invasive, and recurrent disease groups. Tumour recurrence was determined based on regular clinical and radiological data of patients for a mean follow-up of 10 years (SD ± 5.4 years). Phosphoproteomic analyses identified a unique phosphopeptide enrichment pattern which correlates with disease recurrence. Candidate phosphorylated proteins were validated in a large cohort of NF-PitNET patients by western blot and immunohistochemistry. We identified a cluster of 22 phosphopeptides upregulated in recurrent NF-PitNETs compared to non-invasive and invasive subgroups. We reveal significant phosphorylation of the β-catenin at Ser552 in recurrent and invasive NF-PitNETs, compared to non-invasive/non-recurrent NF-PitNET subgroup. Moreover, β-catenin pSer552 correlates with the recurrence free survival among 200 patients with NF-PitNET. Together, our results suggest that the phosphorylation status of β-catenin at Ser552 could act as potential biomarker of tumour recurrence in NF-PitNETs. © 2022, The Author(s).
| Item Type: | Journal Article |
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| Publication: | Acta Neuropathologica Communications |
| Publisher: | BioMed Central Ltd |
| Additional Information: | The copyright for this article belongs to the Authors. |
| Keywords: | beta catenin; phosphopeptide, human; hypophysis tumor; metabolism; neuroendocrine tumor; phosphorylation; tumor recurrence, beta Catenin; Humans; Neoplasm Recurrence, Local; Neuroendocrine Tumors; Phosphopeptides; Phosphorylation; Pituitary Neoplasms |
| Department/Centre: | Division of Biological Sciences > Molecular Biophysics Unit |
| Date Deposited: | 13 Oct 2022 08:17 |
| Last Modified: | 13 Oct 2022 08:17 |
| URI: | https://eprints.iisc.ac.in/id/eprint/77278 |
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