Integrative analysis of KIF4A, 9, 18A, and 23 and their clinical significance in low-grade glioma and glioblastoma

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.

KIF14 and KIF23 Promote Cell Proliferation and Chemoresistance in HCC Cells, and Predict Worse Prognosis of Patients with HCC

“…38,39 Among these hub genes, the kinesin-like protein family has emerged as important regulators in the tumor development and progression. [40][41][42][43][44][45] In this regard, we further examined the biological actions of KIF14 and KIF23 in HCC cells. KIF14 and KIF23 belong to the kinesin-like protein family, which has been shown to play an important role in cancer biology.…”

A role for KIF9 in male fertility

“…In addition, suppression of KIF9 expression has been reported to have effects on spindle dynamics [2]. Intriguingly, KIF9 is overexpressed in glioblastoma and correlates with poor outcome in that disease [3]. Based on our observations that microglia (a macrophage subtype found in the brain) could enhance glioma invasion [4], it is possible that KIF9 plays a role in the aggressiveness of cancer through enabling macrophages to stimulate tumor cell invasion.…”

“…Isolated reports suggest possible associations with Huntington's disease [18] and breast cancer [19]. Interestingly, increased KIF9 expression has been correlated with shorter survival time in glioblastoma including increased EMT and immune function [3]. Further studies will be needed to clarify the function of KIF9 in these pathologies.…”

Systematically Dissecting the Function of RNA-Binding Proteins During Glioma Progression

“…was correlated with cell cycle, G2M checkpoint (Cho et al, 2019). Abrogation of BRCA1 had also been found to play roles in tumor growth in glioma (Rasmussen et al, 2016).…”