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IFN-γ Triggered IFITM2 Expression to Induce Malignant Phenotype in Elderly GBM

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Abstract

Advanced age is an important risk factor for the worse clinical presentation of gliomas, especially glioblastoma (GBM). The tumor microenvironment (TME) in elderly GBM (eGBM) patients is considerably different from that in young ones, which causes the inferior clinical outcome. Based on the data from the Chinese Glioma Genome Atlas RNA sequence (CGGA RNA-seq), the Cancer Genome Atlas RNA array (TCGA RNA-array), and gene set enrichment (GSE) 16011 array sets, the differential genes and function between eGBM (≥ 60 years old) and young GBM (yGBM, 20–60 years old) groups were explored. Immunohistochemistry (IHC) was utilized to depict the abundance of CD8+ cells (the main resource of IFN-γ) and IFITM2 protein expression in GBM samples. Furthermore, reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting (WB) were performed to verify the link between IFN-γ and IFITM2. Moreover, the small-interfering RNA (siRNA) of IFITM2 was used to explore the function of IFITM2 in GBM. Characterized by inflammatory TME and higher IFITM2 expression, eGBM harbored a shorter survival time. Chemotaxis and inflammatory cytokine-related genes were enriched in the eGBM group, with more infiltrative CD8+ T cells. The IHC of CD8 and IFITM2-staining could demonstrate these results. In addition, the IFN-γ response pathway was activated in eGBM and resulted in a dismal outcome. Next, it was found that IFITM2 triggered by IFN-γ played a key role in IFN-γ-induced malignant phenotype in eGBM.

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Availability of Data and Materials

All data and materials used are available from the corresponding author upon reasonable request.

Abbreviations

IFITM2:

Interferon-induced transmembrane 2

TME:

Tumor microenvironment

GBM:

Glioblastoma

yGBM:

Young glioblastoma

eGBM:

Elderly glioblastoma

CNS:

Central nervous system

CCND1:

Cyclin D1

PUMCH:

Peking Union Medical College Hospital

ssGSEA:

Single sample gene set enrichment analysis

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Acknowledgements

The authors thank CGGA, GSE16011, GSE163108, and TCGA sets for the data share and the Beijing Shushi company for data and technology support.

Funding

This work was funded by the Beijing Municipal Natural Science Foundation (7202150) and the National High Level Hospital Clinical Research Funding (2022-PUMCH-A-019) for Yu Wang, and by the National High Level Hospital Clinical Research Funding (2022-PUMCH-B-113), the Tsinghua University-Peking Union Medical College Hospital Initiative Scientific Research Program (2019ZLH101), and the Beijing Municipal Natural Science Foundation (19JCZDJC64200[Z]) for Wenbin Ma.

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Authors and Affiliations

  1. Department of Neurosurgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China

    Tingyu Liang, Yu Wang & Wenbin Ma

  2. Department of Pathology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China

    Xiaoxuan Wang

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  1. Tingyu Liang
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  2. Xiaoxuan Wang
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  3. Yu Wang
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  4. Wenbin Ma
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TYL and XXW drafted the work. TYL and XXW performed the research and analyzed the data. YW and WBM validated the work. All authors read and approved the final manuscript.

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Correspondence to Yu Wang or Wenbin Ma.

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This research was approved by the Institutional Ethics Committee of the Peking Union Medical College Hospital (PUMCH).

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Liang, T., Wang, X., Wang, Y. et al. IFN-γ Triggered IFITM2 Expression to Induce Malignant Phenotype in Elderly GBM. J Mol Neurosci 73, 946–955 (2023). https://doi.org/10.1007/s12031-023-02156-5

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