EFEMP2 indicates assembly of M0 macrophage and more malignant phenotypes of glioma

Abstract

Immune response mediated by macrophages is critical in tumor progression and implicates new targets in potential efficient immunotherapies. Tumor associated macrophages (TAM) are divided into either polarized M1 or M2 phenotype depending on different regulators of polarization and pro- or anti-oncogenic roles they play. Glioma-infiltrated TAMs have been newly reported contrary to the current polarization dogma. Instead, macrophages in glioma exhibit a continuum phenotype between the M1- and M2-like TAM that resembling M0 macrophage. Here we proposed an OS (overall survival)-correlated gene <i>EFEMP2</i> (<i>EGF containing fibulin-like extracellular matrix protein 2</i>) via screening with transcriptional expression levels and methylation data in two glioma databases. <i>EFEMP2</i> was found highly expressed in glioma of higher WHO grade and Mesenchymal subtype glioma, and its transcriptional level could predict OS efficiently in validation datasets. EFEMP2 exhibited a remarkable preference of intercellular expression. In vitro assay showed that EFEMP2's level in medium was closely related to glioma cells' growth. Moreover, <i>EFEMP2</i> expression level was remarkably correlated with immunological responses. M0-like macrophage as a feature of malignancy of glioblastoma revealed distinct assembly in glioma with high level of <i>EFEMP2</i>. These results revealed <i>EFEMP2</i>'s role as a potential characteristic marker of malignant glioma, which are enriched of M0 macrophage.