Cuproptosis key gene FDX1 is a prognostic biomarker and associated with immune infiltration in glioma

Abstract

Recent studies have found that the protein encoded by the FDX1 gene is involved in mediating Cuproptosis as a regulator of protein lipoylation and related to immune response process of tumors. However, the specific biological function of FDX1 in glioma is currently unclear. To explore the potential function of FDX1, this study explored the correlation between the expression of FDX1 in cancers and survival prognosis by analyzing the public databases of GEPIA and Cbioportal. Immune infiltration was analyzed by the TIMER2.0 database in tumors. The possible biological processes and functions of FDX1-related in glioma were annotated through gene enrichment. Relationship between Cuproptosis and autophagy was explored through gene co-expression studies. Summary and conclusions of this study: (1) FDX1 is highly expressed in gliomas and associated with poor prognosis in low-grade gliomas (LGG). (2) Gene annotation indicates that FDX1 is mainly involved in the tumor protein lipoylation and cell death. (3) FDX1 expression is positively correlated with the infiltration of immune cells. (4) LIPT2 and NNAT, two other genes involved in lipoylation, may be unidentified marker gene for Cuproptosis. And the Cuproptosis genes related to FDX1 were positively correlated with the expression of autophagy marker genes Atg5, Atg12, and BECN-1. This evidence suggests that there may be some interaction between FDX1 mediated Cuproptosis and autophagy. In summary, FDX1 may serve as a potential immunotherapy target and prognostic marker for Glioma.

Keywords: Cuproptosis; glioma; immune infiltration; lipoylation; prognostic biomarker.

FIGURE 1

Expression of FDX1 gene in different cancers. (A) Expression of FDX1 gene in different cancer and normal tissues of TIMER2.0 database (*P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001). (B) Expression of FDX1 Transcripts in different cancer and normal tissues in GEPIA database (*P ≤ 0.05, **P ≤ 0.01, ***P ≤ 0.001).

FIGURE 2

Expression level analysis of Fdx1 gene in multiple public databases. (A) Expression of Fdx1 gene in three independent research cohorts of CGGA. (B) Expression of Fdx1 gene in TCGA dataset (LGG-GBM). (C) Expression of FDX1 in glioma cell line U251 cells (the data from Human Protein Altas public database).

FIGURE 3

Expression level analysis of FDX1 in glioma tissue glioma cell lines. (A) Expression of FDX1 protein in Normal and glioma tumor tissue (Grade II, Grade III, and GBM). (B) Statistical analysis of FDX1 protein relative to GAPDH gene expression in normal tissues and glioma tissues. (C) Expression of FDX1 protein in normal glial cell line (NHA cell) and glioma cell lines (U87-MG cell, U251 cell, U373 cell, and A172 cell). (D) Statistical analysis of FDX1 relative to GAPDH gene expression J in glia cell line and glioma cell lines. (E) mRNA expression of FDX1 gene in normal glial cell (NHA cell) and glioma cell lines. (*P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001).

FIGURE 4

Potential prognostic value of FDX1 in glioma. (A) The overall survival and progression-free survival curve of FDX1 in glioma. (B) Survival analysis of glioma in TCGA database. (C) Survival analysis of glioma in CGGA datasets.

FIGURE 5

Genetic alterations and interactions of FDX1 gene in glioma. (A) Genetic alterations of FDX1 gene in cBioPortal database. (B) Mutation frequency of FDX1 gene in GBM and LGG samples. (C) Interaction network analysis of FDX1 gene was performed by GeneMANIA.

FIGURE 6

Co-expression network of FDX1 gene in glioma. (A) The scheme showed FDX1-related differentially expressed genes in glioma. (B) The scheme showed FDX1-related genes in glioma. (C) Genes of FDX1 co-expressed enrichment analysis performed by LinkedOmics (GSEA method).

FIGURE 7

The relationship between FDX1 gene expression and immune infiltration level in glioma. (A) Expression of FDX1 gene related to immune infiltration of CD4 + T cells, Dendritic cells, B cells and macrophage cells in glioma. (B) Analysis between FDX1 gene expression and immune infiltration levels by TISIDB. (C) Correlations between FDX1 gene expression and Dendritic cells, effector memory CD4 T cells, Myeloid-derived suppressor cells and macrophage cells infiltration in glioma.

FIGURE 8

The expression abundance of immune infiltrating cells in Fdx1 high and low expression group was calculated by ssGSEA method (single sample GSEA). P ≤ 0.05, **P ≤ 0.01, and ***P ≤ 0.001.

FIGURE 9

The relationship between FDX1 and immune-related genes expression. (A) The relationship between FDX1 and immunosuppressive genes expression in glioma. (B) The relationship between FDX1 and glioma immunostimulatory genes expression in glioma. (C) The relationship between FDX1 and chemokine genes expression in gliomas. (D) The relationship between FDX1 and receptor genes expression in glioma.

FIGURE 10

Correlation analysis between key Cuproptosis genes, autophagy-related genes and lipoylation genes. (A) Correlation analysis between Fdx1-related Cuproptosis genes and autophagy-related genes. (B) Correlation analysis between Fdx1-related Cuproptosis genes and key genes of protein lipoylation. (C) Illustration of the intersection of identified Cuproptosis and protein lipoylation genes.