Differential gene expression of calcium regulators in distinct subgroups and molecular subtypes of medulloblastoma from publicly available clinical datasets and their correlation with patient survival

Brain tumours are the leading cause of cancer-related death in children and medulloblastoma is the most common malignant childhood brain tumour. Medulloblastoma contains four main molecular subgroups WNT (9%), SHH (29%), Group 3 (19%) and Group 4 (43%). Groups 3 and 4 account for around 60% of all medulloblastomas and are associated with poor survival in patients. Integrative genomic and transcriptomic analysis of medulloblastoma clinical samples has been a subject undergoing intense studies. These studies, have further identified 12 distinct molecular subtypes within medulloblastoma. These discoveries may now help to explain some of the reasons behind the prognostic variability existing among patients. A variety of the cancer hallmarks including proliferation, angiogenesis, migration, invasion, metastasis and therapy resistance are regulated by calcium signalling. The plethora of calcium channels and pumps in the human genome allows nuanced and often localised changes in Ca²⁺ signalling for the specific regulation of cellular processes including those that are hallmarks of cancer. Remodelling of calcium signalling and alterations in the expression of specific calcium channels and pumps have been extensively reported in diverse types of cancer. In this study, using several publically available datasets, a comprehensive study of the expression of calcium regulators in medulloblastoma clinical samples has been performed. This has led to identification of significant expression up-regulation of a plasma membrane cation calcium channel in medulloblastoma and specifically in Subgroups 3 and 4 which occur only in children and are strongly associated with high levels of metastasis and low patient survival. Further studies revealed that this expression is specifically elevated in subtypes 4β and 3γ, both of which are highly metastatic (around 40%) and associated with low patient survival rates of around 70% and 40% respectively. Paediatric medulloblastoma patients with higher expression levels of this Ca²⁺ channel show a trend towards worse survival than patients with lower levels. Further studies are warranted to understand the role of this targetable plasma membrane Ca²⁺ channel in medulloblastoma and the potential of its targeting for the control of medulloblastoma progression and metastasis.