Phosphorylation of β-catenin at Serine552 correlates with invasion and recurrence of non-functioning pituitary neuroendocrine tumours

• DOI: 10.1186/s40478-022-01441-5
• Publication Date: 2022-09-16T21:02:44Z
• Authors: Ashutosh Rai; Soujanya D. Yelam...; Bishan D. Radotra; Sunil K. Gupta; Kanchan K. Mukherjee; Manjul Tripathi; Rajesh Chhabra; Chirag K. Ahuja; Narendra Kumar; Akhilesh Pandey; Márta Korbonits; Pinaki Dutta; Carles Gaston-Mas...
• Keywords: Phosphopeptides; Insulin-like Growth Factors in Health and Disease; Phosphoproteomics; Endocrinology, Diabetes and Metabolism; Western blot; beta-catenin-pSerine552; Cancer research; Prognostic; Pituitary Tumors; Biochemistry; Gene; 03 medical and health sciences; Biochemistry, Genetics and Molecular Biology; Health Sciences; Pathology; Humans; Pituitary Neoplasms; Disease; Transforming Growth Factor Beta Signaling Pathway; Phosphorylation; RC346-429; Diagnosis and Management of Pituitary Disorders; Molecular Biology; Internal medicine; Biology; beta Catenin; 0303 health sciences; Non-functioning pituitary tumours; Research; Cohort; Life Sciences; Biomarker; Immunohistochemistry; Neuroendocrine Tumors; Oncology; Medicine; β-catenin-pSerine552; Neurology. Diseases of the nervous system; Neoplasm Recurrence, Local

AbstractNon-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.