Glioblastoma with PRMT5 gene upregulation is a key target for tumor cell regression

Abstract

Abstract Objectives Protein Arginine Methyltransferase 5 (PRMT5) is an enzyme that regulates gene expression and protein function through arginine methylation. Its association with isocitrate dehydrogenase (IDH) mutation in Grade-4 astrocytoma was rarely investigated. Our aim was to aim to explore the association between IDH mutation and PRMT5 and its effect on tumor recurrence. Methods A retrospective cohort of 34 patients with Grade 4 astrocytoma has been tested for PRMT5 expression using protein and gene expression arrays. The impact of IDH-mutation and PRMT5 expression on tumor recurrence was explored. Results IDH-wildtype was detected in 13 tumors. PRMT5 protein was highly expressed in 30 tumors and the expression was low in four tumors. PRMT5 gene expression was upregulated in 33 tumors and downregulated in a single tumor case. Tumors with different PRMT5 gene expressions and IDH mutation were found to have a significant statistical difference in recurrence-free interval (RFI) (p-value<0.001). IDH-wildtype glioblastoma with upregulated PRMT5 gene or protein expression showed earlier tumor recurrence compared to IDH-mutant Grade 4 astrocytoma with upregulated PRMT5 expression. Conclusions The association between IDH mutation and PRMT5 in IDH-mutant Grade 4 astrocytoma or IDH-wildtype glioblastoma is indirectly bidirectional. PRMT5 upregulation in glioblastoma can lead to increased cell proliferation and tumor regrowth.