Abstract
To determine the prognostic significance of kinesin superfamily gene (KIF) expression in patients with brain cancer, including low-grade glioma (LGG) and glioblastoma (GBM), we comprehensively analyzed KIFs in 515 LGG and 595 GBM patients. Among KIFs, KIF4A, 9, 18A, and 23 showed significant clinical implications in both LGG and GBM. The mRNA and protein expression levels of KIF4A, 9, 18A, and 23 were significantly increased in LGG and GBM compared with those in the normal control groups. The mRNA expression levels of KIF4A, 9, 18A, and 23 in LGG were significantly increased in the high-histologic-grade group compared with those with a low histologic grade. Genomic analysis showed that the percent of mRNA upregulation of KIF4A, 9, 18A, and 23 was higher than that of other gene alterations, including gene amplification, deep deletion, and missense mutation. In addition, LGG patients with KIF4A, 18A, and 23 gene alterations were significantly associated with a poor prognosis. In survival analysis, the group with high expression of KIF4A, 9, 18A, and 23 mRNA was significantly associated with a poor prognosis in both LGG and GBM patients. Gene Set Enrichment Analysis (GSEA) revealed that high mRNA expression of KIF4A, 18A, and 23 in LGG and GBM patients showed significant positive correlations with the cell cycle, E2F targets, G2M checkpoint, Myc target, and mitotic spindle. By contrast, high mRNA expression of KIF9 in both LGG and GBM patients was significantly negatively correlated with the cell cycle, G2M checkpoint, and mitotic spindle pathway. However, it was significantly positively correlated with EMT and angiogenesis. This study has extended our knowledge of KIF4A, 9, 18A, and 23 in LGG and GBM and shed light on their clinical relevance, which should help to improve the treatment and prognosis of LGG and GBM.
Highlights
Glioblastoma (GBM) accounts for 60–70% of all gliomas and remains one of the most challenging malignancies worldwide[1]
We discovered four increased genes, KIF4A, 9, 18A, and 23, which were significantly associated with poor prognosis in low-grade glioma (LGG) and GBM patients
The four kinesin superfamily gene (KIF) in normal glial cells, the glioblastoma cell line, and glioma tissues showed internal discrepancies to identify the targets as nuclear or cytoplasmic especially between the immunofluorescence and immunohistochemistry, KIF4A, 18A, and 23 were able to be identified in nuclear localization, KIF9 was only localized in cytoplasm
Summary
Glioblastoma (GBM) accounts for 60–70% of all gliomas and remains one of the most challenging malignancies worldwide[1]. Secondary glioblastomas can progress from low-grade diffuse astrocytoma or anaplastic astrocytoma[4] Each of these features has demanded the identification of new targets for GBM and LGG for gene/ antibody therapy. The kinesin superfamily genes (KIFs) play important roles related to the cell cycle. They have been shown to participate in chromosomal and spindle movements during mitosis and meiosis. Increasing evidence has indicated that kinesin proteins play critical roles in the genesis and development of human cancers[7]. Several KIF proteins show aberrant overexpression in various cancer cells[7]. KIF4A overexpression has a strong association with the poor prognosis of non-small cell lung cancer[8]. We aimed to determine the prognostic significance of KIF expression in patients with LGG and GBM using TCGA data bioinformatically
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