The present work suggests, for the first time, that PLCβ1 and its downstream pathways could be involved in the aggressiveness of the tumor and could represent possible biomarkers for the molecular stratification of high-grade gliomas, correlating in silico data on glioblastoma patients, data on glioblastoma fresh-frozen samples and molecular data on cellular models engineered for PLCβ1 silencing. The gene discussed is PLCB1; the disease is central nervous system cancer.