Identification of the Key Immune Cells and Genes for the Diagnostics and Therapeutics of Meningioma

Jiawei Chen; Lingyang Hua; Xiupeng Xu; Zeyidan Jiapaer; Jiaojiao Deng; Daijun Wang; Lifeng Zhang; Guoping Li; Ye Gong

doi:10.1016/j.wneu.2023.05.090

Identification of the Key Immune Cells and Genes for the Diagnostics and Therapeutics of Meningioma

World Neurosurg. 2023 Aug:176:e501-e514. doi: 10.1016/j.wneu.2023.05.090. Epub 2023 May 30.

Authors

Jiawei Chen¹, Lingyang Hua¹, Xiupeng Xu², Zeyidan Jiapaer³, Jiaojiao Deng¹, Daijun Wang¹, Lifeng Zhang¹, Guoping Li⁴, Ye Gong⁵

Affiliations

¹ Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; National Center for Neurological Disorders, Shanghai, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China; Neurosurgical Institute of Fudan University, Shanghai, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China.
² Department of Neurosurgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu Province, China.
³ Xinjiang Key Laboratory of Biology Resources and Genetic Engineering, College of Life Science and Technology, Xinjiang University, Urumqi, China.
⁴ Cardiovascular Research Center, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts, USA.
⁵ Department of Neurosurgery, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China; National Center for Neurological Disorders, Shanghai, China; Shanghai Key Laboratory of Brain Function Restoration and Neural Regeneration, Shanghai, China; Neurosurgical Institute of Fudan University, Shanghai, China; Shanghai Clinical Medical Center of Neurosurgery, Shanghai, China; Department of Critical Care Medicine, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China. Electronic address: gong_ye@fudan.edu.cn.

PMID: 37263494
DOI: 10.1016/j.wneu.2023.05.090

Abstract

Background: Dysregulation of immune infiltration critically contributes to the tumorigenesis and progression of meningiomas. However, the landscape of immune microenvironment and key genes correlated with immune cell infiltration remains unclear.

Methods: Four Gene Expression Omnibus data sets were included. CIBERSORT algorithm was utilized to analyze the immune cell infiltration in samples. Wilcoxon test, Random Forest algorithm, and Least Absolute Shrinkage and Selection Operator regression were adopted in identifying significantly different infiltrating immune cells and differentially expressed genes (DEGs). Functional enrichment analysis was performed by Kyoto Encyclopedia of Genes and Genomes and Gene Ontology. The correlation between genes and immune cells was evaluated via Spearman's correlation analysis. Receiver Operator Characteristic curve analysis evaluated the markers' diagnostic effectiveness. The mRNA-miRNA and Drug-Gene-Immune cell interaction networks were constructed to identify potential diagnostic and therapeutic targets.

Results: Plasma cells, M1 macrophages, M2 macrophages, neutrophils, eosinophils, and activated NK cells were the significantly different infiltrating immune cells in meningioma. A total of 951 DEGs, associated with synaptic function and structure, ion transport regulation, brain function, and immune-related pathways, were identified. Among 11 hub DEGs, RYR2 and TTR were correlated with plasma cells; SNCG was associated with NK cells; ADCY1 exhibited excellent diagnostic effectiveness; and ADCY1, BMX, KCNA5, SLCO4A1, and TTR could be considered as therapeutic targets.

Conclusions: ADCY1 can be identified as a diagnostic marker; ADCY1, BMX, KCNA5, SLCO4A1, and TTR are potential therapeutic targets, and their associations with macrophages, neutrophils, NK cells, and plasma cells might impact the tumorigenesis of meningiomas.

Keywords: ADCY1; Differentially expressed genes; Immune cell infiltration; Machine-learning; Meningioma.

MeSH terms

Carcinogenesis
Cell Transformation, Neoplastic
Humans
Meningeal Neoplasms* / diagnosis
Meningeal Neoplasms* / genetics
Meningeal Neoplasms* / therapy
Meningioma* / diagnosis
Meningioma* / genetics
Meningioma* / therapy
MicroRNAs*
Tumor Microenvironment / genetics

Substances

MicroRNAs