Abstract: Objective To investigate neuregulin 2 (NRG2) expression in gliomas and its role in glioma development. Methods We compared the expression levels of NRG2 and glial fibrillary acidic protein (GFAP) in low-grade glioma (LGG) and glioblastoma multiforme (GBM) with those in normal control samples using GEPIA database. The correlation between NRG2 and GFAP expression and their association with the overall survival of patients with LGG and GBM were analyzed. Immunohistochemical staining was used to detect NRG2 protein expression levels in a tissue microarray consisting of human gliomas of different grades, and potential co-localization of NRG2 and GFAP was analyzed using a double-labeling immunofluorescence assay. Western blotting was used to investigate the effect of perifosine (an AKT inhibitor) on the regulation of GFAP expression by NRG2 in human glioblastoma U-87 MG cells. Results Both LGG and GBM tissues, especially the former, exhibited high expressions of NRG2 (P<0.01). In GBM samples, patients with low NRG2 levels had slightly higher overall survival after 30 months than patients with high NRG2 levels. The expression level of NRG2 mRNA was negatively correlated with that of GFAP in LGG samples (P<0.01) but positively correlated with GFAP expression in GBM samples (P< 0.01). Immunofluorescence assay showed that NRG2 and GFAP were co-expressed in the same tumor cells of LGG tissues but were separately expressed in different tumor cells in GBM tissues. In U-87 MG cells, treatment with recombinant human NRG2 obviously promoted the expression of GFAP, and this effect was significantly inhibited by perifosine (P<0.01). Conclusion NRG2 is highly expressed in gliomas of different grades and regulates GFAP expression in glioma cells at least partly via the Akt signaling pathway to affect the survival of glioma patients.

Key words: glioma; neuregulin 2; glial fibrillary acidic protein; low-grade glioma; glioblastoma multiforme