KIF3C is associated with favorable prognosis in glioma patients and may be regulated by PI3K/AKT/mTOR pathway

J Neurooncol. 2020 Feb;146(3):513-521. doi: 10.1007/s11060-020-03399-7. Epub 2020 Feb 4.

Abstract

Purpose: Glioma is the most common malignant primary tumor in the central nervous system (CNS). KIF3C, a motor protein of the kinesin superfamily, is highly expressed in the CNS. Although KIF3C has been identified as a potential therapeutic target in malignant cancers, the expression and function of KIF3C in glioma remains unclear.

Methods: The clinical characteristics of 53 patients with graded glioma (WHO I-IV) were analyzed in this study. The expression of KIF3C in glioma was evaluated by immunohistochemistry (IHC). Survival analysis was compared between higher and lower KIF3C expression groups. Data regarding the expression of KIF3C and survival analysis were also confirmed using the database from The Cancer Genome Atlas (TCGA). The potential mechanism of the regulation of tumor growth by KIF3C was investigated by an analysis of the public database from Oncomine.

Results: Expression of the KIF3C protein was higher in the low-grade glioma (LGG) group (n = 20) than that in the high-grade glioma (HGG) group (n = 33) (P < 0.05). Glioma patients with higher expression of KIF3C had longer survival time (P < 0.05). The subgroup analysis showed that higher KIF3C expression predicted longer survival time in the LGG group (P < 0.05). These clinical results were consistent with those in the TCGA database. Bioinformatics analysis showed that the KIF3C mRNA expression was upregulated significantly in response to PI3K/AKT/mTOR pathway inhibition.

Conclusion: This study demonstrated that KIF3C might inhibit glioma growth to prolong survival time by regulating the PI3K/AKT/mTOR pathway, providing a potential therapeutic target in glioma.

Keywords: Glioma; KIF3C; Survival; TCGA.

MeSH terms

  • Adult
  • Brain Neoplasms / diagnosis*
  • Brain Neoplasms / metabolism*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Glioma / diagnosis*
  • Glioma / metabolism*
  • Humans
  • Kinesins / metabolism*
  • Male
  • Middle Aged
  • Phosphatidylinositol 3-Kinases / metabolism
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction*
  • Survival Analysis
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • KIF3C protein, human
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Kinesins