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Correlation of AIF-1 Expression with Immune and Clinical Features in 1270 Glioma Samples

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Abstract

AIF-1 gene is surrounded by the genes involved in the inflammatory response and located in the major histocompatibility complex (MHC) class III genomic region. It has been found that microglial cells expressed the AIF-1 gene during all stages of mice brain development. However, the role of AIF-1 remains unclear in glioma. A total of 1270 glioma patients from three independent data sets were enrolled in the study. TIMER platform was used for comprehensive molecular characterization of tumor immune infiltrates. Sangerbox was used to analyze AIF-1 RNA sequencing expression data of tumors and normal samples, and to evaluate the association between AIF-1 expression and 29 sub-populations of immune cells. The R language 3.63 was used to identify differentially expressed genes for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Kaplan–Meier survival analysis and univariate/multivariate Cox analysis were used to examine survival distributions. We found that AIF-1 gene was prominently up-regulated, especially in brain glioma including LGG and GBM. A strong correlation was observed between AIF-1 expression and the majority of immune cells, particularly in macrophage, myeloid-derived suppressor cells. Moreover, AIF-1 expression was correlated with immune infiltration level. We found that AIF-1 expression was strongly correlated with the specific immune and prognostic cell markers of monocytes, microglia and macrophages, M1 macrophages, and M2 macrophages after normalization through tumor purity in TCGA-LGG and TCGA-GBM. Higher expression level of AIF-1 was found to be significantly correlated with poor prognosis. GO analysis and KEGG pathways indicated that AIF-1 could affect glioma-related immune activities. Our study suggests that AIF-1 can be treated as a prognostic biomarker for glioma patients. AIF-1 was involved in pro-tumor processes and the regulation of immune status and correlates with poor prognosis.

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Availability of Data and Materials

All data generated or analyzed during this study are obtained from TCGA dataset (https://portal.gdc.cancer.gov/), CGGA dataset (http://cgga.org.cn/), and GSE16011 (https://www.ncbi.nlm.nih.gov/geo/).

Abbreviations

AIF-1:

Allograft inflammatory factor-1

MHC:

Major histocompatibility complex

GO :

Gene Ontology

KEGG :

Kyoto Encyclopedia of Genes and Genomes

CNS:

Central nervous system

TCGA:

The Cancer Genome Atlas

CGGA:

Chinese Glioma Genome Atlas

GTEx:

Genotype-tissue expression

DCs:

Dendritic cells

MDSC:

Myeloid-derived suppressor cells

GAMs :

Glioma-associated macrophages and microglia

TME :

Tumor microenvironment

DEGs:

Differentially expressed genes

CC:

Cellular component

MF :

Molecular function

BP:

Biological process

LGG:

Lower grade glioma

GBM:

Glioblastoma multiforme

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Acknowledgements

The authors would like to thank the TCGA and CGGA databases for the availability of the data.

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Author notes

  1. Minchao Rao, Zihui Yang contributed equally to this paper.

Authors and Affiliations

  1. Department of Oncology, Shangrao People’s Hospital, Shangrao, Jiangxi, China

    Minchao Rao & Kairong Huang

  2. Department of Obstetrics and Gynecology, School of Clinical Medicine, Beijing Tsinghua Changgung Hospital, Tsinghua University, Beijing, 102218, China

    Zihui Yang

  3. Department of Neurosurgery, The First Hospital of Hebei Medical University, Hebei, 050000, China

    Wei Liu

  4. Department of Neurosurgery, School of Medicine, Renji Hospital, Shanghai Jiao Tong University, Shanghai, 200127, China

    Yi Chai

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  1. Minchao Rao
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Contributions

Conception and design: YC, WL, MR. Development of methodology: YC, WL. Acquisition of data: WL. Analysis and interpretation of data: YC, WL, MR. Writing, review and/or revision of the manuscript: MR, YC, KH, ZY. Study supervision: YC. All authors read and approved the final manuscript.

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Correspondence to Wei Liu or Yi Chai.

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This study was approved by Shangrao People’s Hospital (Shangrao, Jiangxi, China). All experiment methods were performed in accordance with the relevant guidelines and regulations.

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All co-authors have given their consent for publication.

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The authors declare no competing interests.

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Rao, M., Yang, Z., Huang, K. et al. Correlation of AIF-1 Expression with Immune and Clinical Features in 1270 Glioma Samples. J Mol Neurosci 72, 420–432 (2022). https://doi.org/10.1007/s12031-021-01948-x

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  • DOI: https://doi.org/10.1007/s12031-021-01948-x

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