Overexpression of CCK Neuropeptide in brain is linked to ZBTB20 mutations: potential diagnostic relevance in glioblastoma.

Glioblastoma (GBM), the most malignant central nervous system cancer, has a median survival rate of 14–16 months. GBM patients have a poor prognosis despite rigorous multi-modal treatments like surgical resection, chemotherapy, and radiation. A systematic bioinformatics analysis of GXA gene expression datasets showed thirty-three overexpressed genes in GBM that were enriched in neuroactive ligand receptor interaction. Subsequently, bulk brain tissue gene expression profiling showed high to moderate expression of CCK, VGF, APLN, CNR1, GRIA4, and PDYN in the cortex, frontal cortex-BA9, BA24 region, cerebellar hemisphere, cerebellum, hippocampus, amygdala, basal ganglia, hypothalamus, substantia nigra, and spinal cord. Interesting, the cortex, frontal cortex-BA9, and BA24 regions had unbelievably high CCK expression. Brain cortex and frontal lobe mutational scoring showed significant rates of IDH1 (49%), TERT (25%), SETD2 (17%), and BRAF (9%). We initially confirmed glioblastoma (GBM) malignancy and therapeutic responses to CCK overexpression and IDH1 mutations in cerebral cortex and frontal cortex tissue samples. However, Mann–Whitney analysis revealed ZBTB20 mutations cause CCK expression, not IDH1 mutations. Overall, CCK expression and ZBTB20 mutations may be used in therapeutic treatments as predictive and diagnostic markers. The expression of CCK was not linked with overall survival and excludes its potential application as prognostic biomarker for GBM. This study showed that CCK and ZBTB20 based predictive and diagnostic technologies can improve precision and personalization of targeted cancer therapies for GBM patients. Nevertheless, experimental evidences have yet to reveal additional therapeutically meaningful connections between CCK expression and ZBTB20 mutations.