Six Immune Associated Genes Construct Prognostic Model Evaluate Low-Grade Glioma.

Yin Qiu Tan,Yang Xu,Yun Tao Li,Xue Yang,Hong Bo Zhang,Qian Xue Chen,Ji An Yang,Teng Feng Yan,Bao Hui Liu

doi:10.3389/fimmu.2020.606164

Abstract

BackgroundThe immunotherapy of Glioma has always been a research hotspot. Although tumor associated microglia/macrophages (TAMs) proves to be important in glioma progression and drug resistance, our knowledge about how TAMs influence glioma remains unclear. The relationship between glioma and TAMs still needs further study.MethodsWe collected the data of TAMs in glioma from NCBI Gene Expression Omnibus (GEO) that included 20 glioma samples and 15 control samples from four datasets. Six genes were screened from the Differential Expression Gene through Gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, protein–protein interaction (PPI) network and single-cell sequencing analysis. A risk score was then constructed based on the six genes and patients’ overall survival rates of 669 patients from The Cancer Genome Atlas (TCGA). The efficacy of the risk score in prognosis and prediction was verified in Chinese Glioma Genome Atlas (CGGA).ResultsSix genes, including CD163, FPR3, LPAR5, P2ry12, PLAUR, SIGLEC1, that participate in signal transduction and plasma membrane were selected. Half of them, like CD163, FPR3, SIGLEC1, were mainly expression in M2 macrophages. FPR3 and SIGLEC1 were high expression genes in glioma associated with grades and IDH status. The overall survival rates of the high risk score group was significantly lower than that of the low risk score group, especially in LGG.ConclusionJoint usage of the 6 candidate genes may be an effective method to diagnose and evaluate the prognosis of glioma, especially in Low-grade glioma (LGG).

Highlights

Glioma is the most common primary tumor in central nervous system, accounting for 80% of all malignant brain tumors [1]
We explored the role of SIGLEC1 and FPR3 in the prognosis and immunotherapy of glioma and thought them would be new biomarkers and targets in diagnoses and treatment of glioma
We first screened the Gene Expression Omnibus (GEO) database and collected three datasets of tumor associated microglia/ macrophages (TAMs) in glioma, the GSE80338 and GSE115397 collected CD11b+ microglia/macrophages from glioma and normal brain tissue and sequenced using RNA sequencing, while the GSE135437 was using FACS sorted on lineage-negative live CD45-positive cells and sequenced using the mCEL-Seq2 protocol

Summary

Introduction

Glioma is the most common primary tumor in central nervous system, accounting for 80% of all malignant brain tumors [1]. Modern aggressive comprehensive treatments are improving, the outcome for glioma remains quite poor. Gliomas are complexly composed of diverse malignant cells and nonmalignant cells, whose development in a special environment called tumor microenvironment (TME) [5]. Among the myriad cell types, microglia, and infiltrating macrophages are known as tumor associated microglia/ macrophages (TAMs), accounting for 30%~50% of the glioma mass [6]. Through interactions with neoplastic cells, TAMs provide a tumor-favorable microenvironment that enable glioma to escape immune surveillance, promoting glioma proliferation and metastasis [6]. It is important to improve our understanding of the interactions between glioma and TAMs and to develop more effective treatment strategies. The relationship between glioma and TAMs still needs further study

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Results

Conclusion