Huang Jiehao, Chen Hongwu, Wei Quantang, Zhang Ziheng, Zhong Zhiwei, Xu Yimin
Department of Neurosurgery, The First Affiliated Hospital of Medical College, Shantou University, Shantou, Guangdong 515041, P.R. China.
Oncol Lett. 2017 Mar;13(3):1688-1694. doi: 10.3892/ol.2017.5631. Epub 2017 Jan 23.
The liver kinase B1 (LKB1)/5'-adenosine monophosphate-activated protein kinase pathway has been reported to facilitate glioma cell growth by improving growth conditions. To investigate the clinical significance of LKB1 in human gliomas western blot analysis and quantitative polymerase chain reaction experiments were performed. The present study demonstrated that LKB1 expression was markedly decreased at the messenger RNA and protein levels in 30 freshly prepared glioma tissues, compared with non-neoplastic brain tissues (P<0.001). Subsequently, immunohistochemical analysis demonstrated that LKB1 immunostaining in 180 glioma tissues was significantly decreased compared with that in the corresponding non-neoplastic brain tissues (P<0.001). Notably, this downregulation frequently occurred in high-grade gliomas, and statistical analysis revealed that low LKB1 expression was significantly associated with large tumor size (P=0.02), advanced World Health Organization grade (P=0.006) and low Karnofsky performance scale (P=0.01). The prognostic value of LKB1 expression in patients with glioma was additionally evaluated using Kaplan-Meier survival curves and Cox proportional hazards regression models. As a result, the overall survival time of patients with glioma with low LKB1 expression was shorter compared with that of patients with high LKB1 expression (P<0.001), and low LKB1 expression also indicated decreased survival time in patients with high-grade glioma (P<0.001). Collectively, the present data indicated that the downregulation of LKB1 was closely associated with the malignant degree of human gliomas, exhibiting lower expression at a higher grade. Notably, LKB1 may serve as a potential prognostic biomarker for patients with glioma following surgery.
据报道,肝脏激酶B1(LKB1)/5'-单磷酸腺苷激活的蛋白激酶途径可通过改善生长条件促进胶质瘤细胞生长。为了研究LKB1在人类胶质瘤中的临床意义,进行了蛋白质印迹分析和定量聚合酶链反应实验。本研究表明,与非肿瘤性脑组织相比,30个新鲜制备的胶质瘤组织中的LKB1在信使核糖核酸和蛋白质水平上均显著降低(P<0.001)。随后,免疫组织化学分析表明,与相应的非肿瘤性脑组织相比,180个胶质瘤组织中的LKB1免疫染色显著降低(P<0.001)。值得注意的是,这种下调在高级别胶质瘤中经常发生,统计分析显示,LKB1低表达与肿瘤体积大(P=0.02)、世界卫生组织高级别(P=0.006)和卡氏功能状态评分低(P=0.01)显著相关。还使用Kaplan-Meier生存曲线和Cox比例风险回归模型评估了LKB1表达对胶质瘤患者的预后价值。结果,LKB1低表达的胶质瘤患者的总生存时间比LKB1高表达的患者短(P<0.001),LKB1低表达也表明高级别胶质瘤患者的生存时间缩短(P<0.001)。总体而言,目前的数据表明,LKB1的下调与人类胶质瘤的恶性程度密切相关,在更高级别时表达较低。值得注意的是,LKB1可能作为胶质瘤患者手术后潜在的预后生物标志物。