胶质母细胞瘤中瘤周水肿与程序性细胞因子10的关系  

Correlation between programmed cell death 10 and peritumoral edema in glioblastoma

作　　者：吴思思 刘京典 赵恺[1] 王俊文[1] 胡峰 张所军 牛洪泉[1] 舒凯[1] Wu Sisi;Liu Jingdian;Zhao Kai;Wang Junwen;Hu Feng;Zhang Suojun;Niu Hongquan;Shu Kai(Department of Neurosurgery,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan 430030,China)

机构地区：[1]华中科技大学同济医学院附属同济医院神经外科,武汉430030

出　　处：《中华实验外科杂志》2022年第2期359-361,共3页Chinese Journal of Experimental Surgery

基　　金：湖北省病理生理学会面上项目(2021HBAP007);国家自然科学基金(81602204、81702478、82072805)。

摘　　要：目的探讨程序性细胞因子10(PDCD10)与胶质母细胞瘤(GBM)瘤周水肿(PTE)的关系。方法纳入2017年1月至2021年1月于湖北省华中科技大学同济医学院附属同济医院收治确诊为GBM患者21例。收集GBM患者的磁共振影像学资料和手术标本。采用磁共振T2WI图像进行测量评估PTE宽度。采用慢病毒转染法构建稳定转染的过表达PDCD10的胶质瘤细胞系(U251、U118和GL261细胞)。蛋白质印迹法(Western blot)分别检测U251、U118及GL261细胞系对照组和过表达PDCD10组PDCD10, 水通道蛋白4(AQP4)和水通道蛋白1(AQP1)的表达。通过对照组及过表达PDCD10的GL261细胞系进行雄性裸鼠原位成瘤, 验证PDCD10的表达与PTE, AQP1和AQP4的关系。通过t检验分析两组间差异, 两组间相关性研究使用Pearson′s相关分析。结果 GBM患者PDCD10表达与PTE分级呈正相关(r^(2)=0.871, F=128.3, P<0.01), 且PDCD10与AQP4的表达呈正相关(r^(2)=0.854, F=111.4, P<0.01)。过表达PDCD10的胶质瘤细胞系AQP4的表达显著高于对照组(U251:0.982±0.732比4.402±0.779, t=5.543, P<0.01;U118:4.907±0.027比10.030±1.075, t=8.244, P<0.01;GL261:1.391±0.701比6.638±2.565, t=3.418, P<0.05)。裸鼠原位成瘤实验证实过表达PDCD10的GL261细胞成瘤后PTE的最大截面积显著高于对照组[(16.9±6.7) mm^(2)比(32.3±5.4) mm^(2), t=3.579, P<0.05]。过表达PDCD10胶质瘤成瘤后AQP4表达高于对照组(GL261成瘤组:1.577±0.673比0.564±0.125, t=2.962, P<0.05)。结论 PDCD10可能通过调控AQP4促进胶质瘤PTE。Objective To explore the relationship between programmed cell death 10(PDCD10)and peritumoral edema(PTE)in glioblastoma multiform(GBM).Methods A total of 21 patients diagnosed with glioblastoma admitted to Wuhan Tongji Hospital from January 2017 to January 2021 were included.Data on MRI image and surgical samples of GBM patients were collected.PTE was analyzed on T2WI-MRI.Stable overexpression of PDCD10(oxPDCD10)in human-GBM cell lines(U251,U118 and GL261)was established by lentivirus transduction.The expression of PDCD10,Aquaporin 4(AQP4)and Aquaporin 1(AQP1)in U118,U251 and GL261 cells was detected by Western blotting.GL261 and oxPDCD10-GL261 cells were employed in the orthotopic homograft mouse model to verify the relationship between PDCD10 and PTE,AQP1 and AQP4.The differences between groups were analyzed by t test.Pearson’s relative analysis was used to test the correlation between groups.Results The expression of PDCD10 in GBM patients was positively associated with PTE grade(r^(2)=0.871,F=128.3,P<0.01).Moreover,a positive correlation was detected between the expression of PDCD10 and AQP4(r^(2)=0.854,F=111.4,P<0.01).In vitro experiment indicated that upregulation of PDCD10 in GBM cells increased the expression of AQP4(U251:0.982±0.732 vs.4.402±0.779,t=5.543,P<0.01;U118:4.907±0.027 vs.10.030±1.075,t=8.244,P<0.01;GL261:1.391±0.701 vs.6.638±2.565,t=3.418,P<0.05).In vivo experiment suggested that the PTE area in oxPDCD10-GL261 formed tumors was significantly larger than that of the control group[(16.9±6.7)mm^(2) vs.(32.3±5.4)mm^(2),t=3.579,P<0.05].The expression of AQP4 in oxPDCD10-mice was higher than that of the control group(GL261 groups:1.577±0.673 vs.0.564±0.125,t=2.962,P<0.05).Conclusion Our current study demonstrates that PDCD10 increases PTE in GBM most likely through the regulation of AQP4 signaling.

关 键 词：胶质母细胞瘤 程序性细胞因子10 瘤周水肿 水通道蛋白4 

分 类 号：R739.41[医药卫生—肿瘤]