CALB1 expression in meningioma: associations with progression-free survival and chromosome arm 6q loss

Molecular profiling has refined risk stratification in meningioma, but the biological relevance of associated transcriptional changes remains incompletely understood. Calbindin D28K (Calb), encoded by CALB1 , is a calcium-binding protein with reported anti-apoptotic and cytoprotective functions. Previous unsupervised transcriptomic analysis identified CALB1 upregulation in meningiomas with aggressive cellular features, but its biological and clinical relevance remains unresolved. We analysed Calb immunoreactivity in 231 meningioma tissue microarray (TMA) cores from 147 patients and evaluated CALB1 transcript expression, DNA methylation and copy-number alterations in an independent cohort of 110 primary meningiomas. Calb immunoreactivity was detected in approximately 30% of primary tumours, and elevated CALB1 transcript levels were observed at a similar frequency in the molecular cohort. High Calb protein expression was associated with shorter progression-free survival (PFS) after adjustment for the included clinical variables in the primary cohort. This association was also observed in restricted analyses of histological WHO grade 2 meningiomas. Lower methylation of selected exonic and intronic CALB1 CpG sites correlated with a higher transcript expression, consistent with an epigenetic contribution to deregulation. Multivariable analyses identified associations of CALB1 transcript expression with chromosome arm 6q loss, histological WHO grade, CALB1 hypo-methylation and specific methylation subclasses in the secondary cohort. Differential expression analysis of tumours harbouring 6q loss identified expression differences in CALB1 and transcription factors, including NKX2-5 and SOX11 . In contrast, expression of a related calcium-binding protein Calretinin (Calr) and the Progesterone Receptor (PR) was not significantly associated with PFS in the primary cohort. Together, these findings support the potential prognostic relevance of Calb protein expression, particularly in histological WHO grade 2 meningiomas, and associate CALB1 transcript expression with selected molecular features in complementary cohorts. Calb immunohistochemistry may therefore provide a practical tool for refining risk stratification in this clinically heterogeneous tumour type prior to integrative molecular testing.