ANXA1 as a Prognostic and Immune Microenvironmental Marker for Gliomas Based on Transcriptomic Analysis and Experimental Validation.

Zhongxiao Lin,Hua Wang,Xiao Lin,Kankai Wang,Ying Zhang,Min Wen,Qichuan Zhuge,Su Yang,Hengli Zhang,Junnan Ru,Chaojie Yao,Enxing Yu,Jiayu Chen,Lijie Huang

doi:10.3389/fcell.2021.659080

Abstract

The tumor microenvironment (TME) plays an important role in the growth and invasion of glioma. This study aimed to analyze the composition of the immune microenvironment in glioma samples and analyze the important differentially expressed genes to identify novel immune-targeted therapy for glioma. We downloaded transcriptomic data of 669 glioma samples from The Cancer Genome Atlas database. CIBERSORT and ESTIMATE methods were used to calculate the proportion of tumor-infiltrating immune cells and ratio of immune and stromal components in the TME. The differentially expressed genes (DEGs) were screened by comparing the genes expressed by both stromal and immune cells. Annexin A1 (ANXA1) was determined to be an important prognostic indicator through the common overlap of univariate Cox regression analysis and protein–protein interaction network analysis. The proportion of tumor-infiltrating immune cells, calculated by CIBERSORT algorithm, had a significant difference in distribution among the high and low ANXA1 expression groups, indicating that ANXA1 could be an important immune marker of TME. Furthermore, ANXA1 level was positively correlated with the histopathological factors and negatively related to the survival of glioma patients based on the analysis of multiple databases. Finally, in vitro experiments verified that antagonizing ANXA1 expression promoted cell apoptosis and inhibited the invasion and migration capacities of glioma cells. Therefore, ANXA1 due to its immune-related functions, can be an important prognostic indicator and immune microenvironmental marker for gliomas. Further studies are warranted to confirm ANXA1 as a potential immunotherapeutic target for gliomas.

Highlights

MATERIALS AND METHODSGlioma is the most common primary intracranial tumor, characterized by high recurrence, easy invasion, and high mortality (Ostrom et al, 2014)
Previous studies have shown that therapies targeting the tumor microenvironment have achieved good results, such as anti-programmed death-ligand 1 therapy (Ruan et al, 2019; Ene et al, 2020) and T cell immunotherapy (Brown et al, 2016; Choi et al, 2019)
Upon evaluating the glioma samples in the The Cancer Genome Atlas (TCGA) database, our results showed that the immune components in tumor microenvironment (TME) contributed to the prognosis of glioma

Summary

Introduction

MATERIALS AND METHODSGlioma is the most common primary intracranial tumor, characterized by high recurrence, easy invasion, and high mortality (Ostrom et al, 2014). The microenvironment of glioma is composed of tumor cells, immune cells, stromal cells, and their various secreted factors. TME is the basis of tumor pathogenesis and is an important therapeutic target (Wood et al, 2014; Schulz et al, 2019). Previous studies have shown that the stromal cells in the TME are conducive to the tumor growth and invasion, and have an anti-tumor immune effect (Guo and Deng, 2018; Giraldo et al, 2019). Immune cells, such as T cells and M1 and M2 macrophages, play a key role in the anti-tumor response (Bamodu et al, 2019; Heymann et al, 2019). There is need to identify novel therapeutic targets to develop improved therapies with higher efficacy

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