Department of Neurosurgery, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, 200032, China.
Department of Nuclear Medicine, Shanghai Tenth People's Hospital, Tongji University, Shanghai, 200072, China.
J Neurooncol. 2020 Feb;146(3):513-521. doi: 10.1007/s11060-020-03399-7. Epub 2020 Feb 4.
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.
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.
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.
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.
神经胶质瘤是中枢神经系统(CNS)最常见的恶性原发性肿瘤。驱动蛋白家族的马达蛋白 KIF3C 在中枢神经系统中高度表达。虽然 KIF3C 已被确定为恶性癌症的潜在治疗靶点,但 KIF3C 在神经胶质瘤中的表达和功能仍不清楚。
本研究分析了 53 例分级神经胶质瘤(WHO I-IV)患者的临床特征。通过免疫组织化学(IHC)评估 KIF3C 在神经胶质瘤中的表达。在更高和更低的 KIF3C 表达组之间比较生存分析。还使用癌症基因组图谱(TCGA)数据库的数据来验证 KIF3C 的表达和生存分析。通过对 Oncomine 公共数据库的分析,研究了 KIF3C 调节肿瘤生长的潜在机制。
KIF3C 蛋白在低级别神经胶质瘤(LGG)组(n=20)中的表达高于高级别神经胶质瘤(HGG)组(n=33)(P<0.05)。KIF3C 表达较高的神经胶质瘤患者的生存时间更长(P<0.05)。亚组分析显示,KIF3C 表达较高预测 LGG 组的生存时间更长(P<0.05)。这些临床结果与 TCGA 数据库一致。生物信息学分析表明,PI3K/AKT/mTOR 通路抑制可显著上调 KIF3C mRNA 表达。
本研究表明,KIF3C 可能通过调节 PI3K/AKT/mTOR 通路抑制神经胶质瘤生长,从而延长生存时间,为神经胶质瘤提供了一个潜在的治疗靶点。