Research Paper|Volume 12, Issue 9|pp 8397—8412

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

Lijie Huang^1,^2,^3,^4,⁵, Zheng Wang^1,^2,^3,^4,⁵, Yuanhao Chang^1,^2,^3,^4,⁵, Kuanyu Wang^1,^2,^3,^4,⁵, Xun Kang^1,^2,^3,^4,⁵, Ruoyu Huang^1,^2,^3,^4,⁵, Ying Zhang^1,^2,^3,^4,⁵, Jing Chen^1,^2,^3,^4,⁵, Fan Zeng^1,^2,^3,^4,⁵, Fan Wu^1,^2,^3,^4,⁵, Zheng Zhao^1,^2,^3,^4,⁵, Guanzhang Li^1,^2,^3,^4,⁵, Hua Huang^1,^2,^3,^4,⁵, Tao Jiang^1,^2,^3,^4,⁵, Huimin Hu^1,^2,^3,^4,⁵

¹Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, Beijing, China
²Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
³Center of Brain Tumor, Beijing Institute for Brain Disorders, Beijing, China
⁴China National Clinical Research Center for Neurological Diseases, Beijing, China
⁵Chinese Glioma Genome Atlas Network (CGGA), Beijing, China

Received: April 27, 2019Accepted: February 19, 2020Published: May 12, 2020

https://doi.org/10.18632/aging.103147

Copyright © 2020 Huang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

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 EFEMP2 (EGF containing fibulin-like extracellular matrix protein 2) via screening with transcriptional expression levels and methylation data in two glioma databases. EFEMP2 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, EFEMP2 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 EFEMP2. These results revealed EFEMP2’s role as a potential characteristic marker of malignant glioma, which are enriched of M0 macrophage.