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FBP1 is a potential prognostic biomarker and correlated with tumor immunosuppressive microenvironment in glioblastoma

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Abstract

Hypoxia has been shown to contribute to tumor immunosuppressive microenvironment and is an effective prognostic indicator. This study aimed to screen prognostic hypoxia-related genes (HRGs) in glioblastoma and investigate the association between HRGs and tumor immunosuppressive microenvironment. The glioblastoma-related mRNA data were collected from TCGA, GEO, and CGGA databases. Totally 200 HRGs were obtained from the GSEA website. The prognostic HRGs were screened by univariate Cox regression analysis. Somatic mutation data of glioblastoma from TCGA was visualized using the “maftools” of R package. Immune cell infiltration proportions were calculated by CIBERSORT. The TISIDB online tool was applied to analyze the relationship between HRGs and immunoinhibitors as well as the HRG expression in different glioblastoma immune and molecular subtypes. Hub gene’s mRNA and protein levels in cell lines were determined by qRT-PCR and western blot, respectively. The effects of hub gene knockdown on cell viability and migration ability were evaluated employing CCK8 and wound healing assays. The univariate Cox regression showed that high level of FBP1 (fructose-1,6-bisphosphatase 1) was a poor prognostic biomarker, and FBP1 was mainly expressed in lymphocyte depleted immune subtype of glioblastoma. High FBP1 mRNA and protein levels have been successfully validated in vitro. The somatic mutation analysis suggested that TP53 mutation rate was the highest in the high FBP1 glioblastoma group, while EGFR mutation rate was the highest in the low FBP1 glioblastoma group. In the high FBP1 group, the infiltration proportions and types of immune cells were less, dominated by macrophages M2, and the expression of CTLA4, LAG3, TIGIT, PDL1, and PDL2 was significantly upregulated. The expression of FBP1 was positively correlated with several immunoinhibitors, such as IL-10 and TGFβ-1. In conclusion, we demonstrated that FBP1 could serve as a prognostic biomarker for glioblastoma. The immune microenvironment in the high FBP1 group might be suppressed by up-regulating immune checkpoints and immunoinhibitors.

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Data availability

The datasets generated and analyzed during the current study are available in the The Cancer Genome Atlas (TCGA) repository (https://tcga-data.nci.nih.gov/tcga/), the Gene Expression Omnibus database (GEO, http://www.ncbi.nlm.nih.gov/geo/, accession number GSE4290 and GSE4412), and the Chinese Glioma Genome Atlas (CGGA, http://www.cgga.org.cn/).

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Funding

This work was supported by the Medical and Health Technology Development Plan Project of Shandong Province [grant number 2019WS308].

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Authors and Affiliations

  1. Department of Neurosurgery, Zibo Central Hospital, 255000 Zibo, Shandong, China

    Hu Sun, Lijie Jing & Hao Zhao

  2. Department of Cardiology, Zibo Central Hospital, 255000 Zibo, Shandong, China

    Hui Zhang

  3. Department of Neurosurgery, The Affiliated Hospital of Qingdao University, No. 1677 Wutaishan Road, Huangdao District, Qingdao, 266000, Shandong, China

    Bing Chen

  4. Department of Breast and Thyroid Surgery, Zibo Central Hospital, No. 54 Gongqingtuan West Road, 255000 Zibo, Qingdao, Shandong, China

    Wei Song

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  1. Hu Sun
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  4. Hao Zhao
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  5. Bing Chen
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Contributions

(I) Conception and design: Hu Sun

(II) Administrative support: Bing Chen, Hu Sun, and Hui Zhang

(III) Provision of study materials or patients: Hui Zhang

(IV) Collection and assembly of data: Hao Zhao, Hu Sun, and Wei Song

(V) Data analysis and interpretation: Hao Zhao, Hu Sun, and Wei Song

(VI) Manuscript writing: all authors

(VII) Final approval of manuscript: all authors

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Correspondence to Bing Chen or Wei Song.

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Supplementary information

ESM 1

Figure S1 A-B Expression levels of FBP1 under different CNV and FBP1 mutations.

ESM 2

Table S1 200 hypoxia-related genes obtained from the GSEA website.

ESM 3

Table S2 GSEA enrichment analysis revealed immune-related pathways enriched in the FBP1 high expression group.

ESM 4

Table S3 GO annotation of 281 genes in three immune-related pathways.

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Sun, H., Zhang, H., Jing, L. et al. FBP1 is a potential prognostic biomarker and correlated with tumor immunosuppressive microenvironment in glioblastoma. Neurosurg Rev 46, 187 (2023). https://doi.org/10.1007/s10143-023-02097-y

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