B3GNT5 is a novel marker correlated with stem-like phenotype and poor clinical outcome in human gliomas.

Glioblastoma multiforme (GBM) is the most lethal tumor with a median patient survival of 14 to 15 months. Glioma stem cells (GSCs) play a critical role in tumor initiation and therapeutic resistance in GBM. B3GNT5 has been suggested as the key glycosyltransferase in the biosynthesis of the (neo-) lacto series of glycosphingolipid. In this study, we evaluated the B3GNT5 expression in GSCs as well as the correlation with clinical data in GBM. The mRNA levels of B3GNT5 in normal astrocytes, four glioma cell lines, and four GSCs were evaluated using real-time PCR. Small interference RNAs (siRNAs) were used to inhibit B3GNT5 expression and analyze its ability to form neurospheres. Statistical analyses were conducted to determine the association with B3GNT5 expression and tumor grade and GBM subtypes as well as patient survival using public datasets. B3GNT5 expression was significantly elevated in GSCs compared with normal astrocytes, glioma cell lines, and their matched differentiated tumor cells. Knockdown of B3GNT5 in GSCs decreased the neurosphere formation. Patients with high B3GNT5 expression had a short overall survival. B3GNT5 is correlated with classical and mesenchymal GBM subtypes. The findings suggest the central role of B3GNT5 in regulating malignancy of GBM.