切换至 "中华医学电子期刊资源库"

中华神经创伤外科电子杂志 ›› 2021, Vol. 07 ›› Issue (04) : 224 -234. doi: 10.3877/cma.j.issn.2095-9141.2021.04.008

基础研究

Kir4.1在恶性胶质瘤中的表达及其潜在作用:数据库结合文献分析
张婵1, 薛强2, 田锐锋3, 陈晓燕4,()   
  1. 1. 710032 西安,空军军医大学附属第一医院门诊部
    2. 710032 西安,空军军医大学附属第一医院心内科
    3. 710032 西安,空军军医大学附属第一医院感染科
    4. 710032 西安,空军军医大学附属第一医院神经外科
  • 收稿日期:2021-03-26 出版日期:2021-08-11
  • 通信作者: 陈晓燕

Expression and potential role of Kir4.1 in malignant gliomas: database combined with document analysis

Chan Zhang1, Qiang Xue2, Ruifeng Tian3, Xiaoyan Chen4,()   

  1. 1. Department of Outpatient, The First Affiliated Hospital of Air Force Medical University, Xi’an 710032, China
    2. Department of Cardiology, The First Affiliated Hospital of Air Force Medical University, Xi’an 710032, China
    3. Department of Infection, The First Affiliated Hospital of Air Force Medical University, Xi’an 710032, China
    4. Department of Neurosurgery, The First Affiliated Hospital of Air Force Medical University, Xi’an 710032, China
  • Received:2021-03-26 Published:2021-08-11
  • Corresponding author: Xiaoyan Chen
引用本文:

张婵, 薛强, 田锐锋, 陈晓燕. Kir4.1在恶性胶质瘤中的表达及其潜在作用:数据库结合文献分析[J/OL]. 中华神经创伤外科电子杂志, 2021, 07(04): 224-234.

Chan Zhang, Qiang Xue, Ruifeng Tian, Xiaoyan Chen. Expression and potential role of Kir4.1 in malignant gliomas: database combined with document analysis[J/OL]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2021, 07(04): 224-234.

目的

探究内向整流钾通道Kir4.1在恶性胶质瘤中的表达情况,通过数据库并结合文献分析其与胶质瘤癫痫、水肿等症状的相关性及其相关机制。

方法

利用Oncomine数据库分析TCGA数据集中胶质母细胞瘤与正常脑组织相比的表达情况,收集临床不同级别胶质瘤患者的标本及病理信息,分析不同级别胶质瘤中Kir4.1的表达情况。利用cBioPortal数据库分析胶质瘤中Kir4.1突变情况。

结果

Oncomine数据库因数据集样本量差异而显示出较大的结果差异性,RT-PCR和免疫组化显示高级别胶质瘤比低级别胶质瘤的Kir4.1表达量更少,但是低级别胶质瘤的Kir4.1表达量比正常脑组织表达量高,差异具有统计学意义(P<0.05)。cBioPortal数据库显示Kir4.1突变概率在胶质母细胞瘤中极低,部分基因组改变与突变数量之间差异均有统计学意义(P<0.05)。MSH2ERRFI1CTNNB1SEPRINE1FOXM1RAD50等基因在改变组中高表达,INPP4BXBP1AXL等基因在非改变组里高表达。

结论

Kir4.1在不同级别的胶质瘤中表达具有差异性,高级别的胶质瘤具有更低的Kir4.1的表达量,且Kir4.1的表达可能和高级别胶质瘤患者发生癫痫、水肿等临床症状相关,为未来探索Kir4.1在胶质母细胞瘤中的潜在机制提供了新的思路。

Objective

To explore the expression of inward rectifier potassium channel Kir4.1 in malignant gliomas and its correlation and correlation mechanism with epilepsy, edema and other symptoms of gliomas through database and document analysis.

Methods

Oncomine database was used to analyze the expression of glioblastoma compared with normal brain tissue in TCGA data set. Specimens and pathological information of patients with different clinical grades of glioma were collected to analyze the expression of Kir4.1 in different grades of glioma. Kir4.1 mutations in gliomas were analyzed by cbioportal database.

Results

The results of oncomine database showed great differences due to the differences of sample size. RT-PCR and immunohistochemistry showed that the expression of Kir4.1 in high-grade glioma was less than in low-grade glioma, but the expression of Kir4.1 in low-grade glioma was higher than in normal brain tissues, and the difference was statistically significant (P<0.05). The cbioportal database showed that the mutation probability of Kir4.1 was extremely low in glioblastoma, and the difference between partial genome alteration and the number of mutations was statistically significant (P<0.05). MSH2, ERRFI1, CTNNB1, SEPRINE1, FOXM1, RAD50 and other genes were highly expressed in the altered group, while INPP4B, XBP1, AXL and other genes were highly expressed in the non-altered group.

Conclusion

The expression of Kir4.1 is different in different grades of glioma. High grade glioma has lower expression of Kir4.1, and the expression of Kir4.1 may be related to epilepsy, edema and other clinical symptoms in patients with high grade glioma, which provides a new idea for exploring the potential mechanism of Kir4.1 in glioblastoma in the future.

图1 Oncomine数据库TCGA Brain数据集中Kir4.1/KCNJ10表达情况
图2 胶质瘤临床标本和正常脑组织的HE染色
图3 胶质瘤临床标本和正常脑组织中的Kir4.1/KCNJ10表达
表1 Ⅱ级胶质瘤患者病理信息
序号 ATRX BRAF CD34 EGFR EMA GFAP Ki67 NF MGMT Neun Olig-2 P53 S-100 Syn Vim 1P 19q IDH1 IDH 级别
P1     - - - + 5% + -   + - + - -     R132H+  
P2 ±         + 5%   -   + ± + - - 缺失 缺失 R133H突变  
P3     - + - + 12%   -   + -   + -     R132H+  
P4         - + 20-30% +       - +   +        
P5 + VE1(-) 血管+   - 星形象胞+ (+,局部约20%) +   残余神经元+ + (+,约10%) + +   缺失 缺失    
P6           +             + 灶+          
P7           + 6%           + +          
P8 灶+ VE1(-) 血管+   - + 2% + - + +   + - -     R132H(-)  
P9 + VE1(-) - + - + 8% + (+,约5%)   + 散在+ + - - 缺失 缺失 R132H突变  
P10 + VE1(-) - + - + 6% + +   + - + 灶+ - 缺失 缺失 R132H(+) 突变
P11 + VE1(-) - + - + 2% + (+,约10%) 节细胞+ + 灶+ + + - 缺失 缺失 R132H(+) 突变
P12 + VE1(-) 血管+ + - + (+,局部约5%)   (+,约15%)   + - + - - 缺失 缺失 R132H突变 突变
P13 + VE1(-) -   - + (+,约4%) - (+,约10%)   + - + - - 缺失 缺失 R132H突变 突变
P14 局部+ VE1(-) - + - + 15%       + 散在+ + 部分+ - 缺失 缺失 R132H突变 突变
P15 + V600E(-) - + - + (+,局部约15%) - -   + 少数+ + + - 缺失 缺失 + 突变
P16 + V600E(-) - + - + (+,约15%) - 部分-,检测到基因启动子区甲基化水平为43%+   + - + + - 缺失 缺失 + 突变
P17     -     + 2%   + - +   + + +        
P18 部分+   血管+   - + (+,局部约6%) + -   + - + + + 缺失 缺失 R132H(-) 突变
P19 +   -   灶+ + 12% 小灶弱+ -   +   + 小灶+ - 缺失 缺失 R132H(+) 突变
P20           + (+,局部约8%)   -                    
表2 Ⅳ级胶质瘤患者病理信息
序号 ATRX BRAF CD34 EGFR EMA GFAP Ki67 NF MGMT Olig-2 P53 S-100 Syn Vim 19q IDH1 IDH 级别
P1 +   血管+ 小灶+ - - 15% - - - - 灶+ - 弱+     野生型
P2 + VE1(-) 血管+ + - + 15% - - + 异常膜+ + 弱+ + 缺失   野生型
P3 部分+   -   - + 局部60% + + + 部分+ + 灶+ 0   R132H(-) 野生型
P4 + VE1(-) 血管+ + - + 15% - - + 异常膜+ + 弱+ + 缺失   野生型
P5 - VE1(-) - + - + 40% - ± (+/-) (-/+) + - (+/-)     H3K27M突变型
P6 +   -     + 80% - - + + + 弱+ -     野生型
P7 -   - + - + 30% - - + 散在+ + - -     野生型
P8 +   -     + 80%   ± + + + - 散在+   R132H(-) 野生型
P9 + VE1(-) 血管+ - - + 45%   <5% + 野生型 + + +     野生型
P10 + VE1(-) - + - + 40% - +,约40% + + + - -   R132H(-) 野生型
P11 - VE1(-) - + - 局灶+ 70% - ± - 弥漫强+ 局灶+ - +     胶质母细胞瘤
P12 +   -   - 灶+ 60% - - + +,突变型表达 + 小灶+ -     野生型
P13   VE1(-) 显示血管增生 + - + 60% - +,约5% + 弥漫+,突变型表达 + - -     IDH1/2野生型
P14 +   + + 局部+ + +,局部约35% - - 局部+ - + - +     野生型
P15 +   -   - + 60% - - + 弥漫强+ + - +     野生型
P16 + VE1(-) - + - + +,15% - - + + + - +   R132H(-) 野生型
P17 -   -   ± + 40% + +,15% + + + - +     IDH1突变型
P18 + VE1(-) - - - + 30% + - + + + - +     野生型
P19 - VE1(-) - - - + 30% - - + 散在+ + 局部+ +     野生型
P20 + VE1(-) - + - - 50% - - + 灶+ + - +   R132H(-) 野生型
图4 cBioPortal数据库检索Kir4.1/KCNJ10突变情况
表3 改变组和非改变组之间基因表达差异
图5 不同表达Kir4.1患者的总生存率和无病生存期分析
图6 Kir4.1相关蛋白KEGG/GO分析
[1]
Larjavaara S, Mäntylä R, Salminen T, et al. Incidence of gliomas by anatomic location[J]. Neuro Oncol, 2007, 9(3): 319-325.
[2]
Kerkhof M, Vecht CJ. Seizure characteristics and prognostic factors of gliomas[J]. Epilepsia, 2013, 54 Suppl 9: 12-17.
[3]
Stupp R, Hegi ME, Mason WP, et al. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial[J]. Lancet Oncol, 2009, 10(5): 459-466.
[4]
Bauchet L, Mathieu-Daudé H, Fabbro-Peray P, et al. Oncological patterns of care and outcome for 952 patients with newly diagnosed glioblastoma in 2004[J]. Neuro Oncol, 2010, 12(7): 725-735.
[5]
Higashimori H, Sontheimer H. Role of Kir4.1 channels in growth control of glia[J]. Glia, 2007, 55(16): 1668-1679.
[6]
Tang X, Schmidt TM, Perez-Leighton CE, et al. Inwardly rectifying potassium channel Kir4.1 is responsible for the native inward potassium conductance of satellite glial cells in sensory ganglia[J]. Neuroscience, 2010, 166(2): 397-407.
[7]
Wu P, Su XT, Gao ZX, et al. Renal tubule Nedd4-2 deficiency stimulates Kir4.1/Kir5.1 and thiazide-sensitive NaCl cotransporter in distal convoluted tubule[J]. J Am Soc Nephrol, 2020, 31(6): 1226-1242.
[8]
肖宇,孟欣欣,张昊, 等. 肾小管管周膜Kir4.1及Kir4.1/Kir5.1通道的功能及调控[J]. 生理学报, 2018, 70(6): 600-606.
[9]
Zurolo E, de Groot M, Iyer A, et al. Regulation of Kir4.1 expression in astrocytes and astrocytic tumors: a role for interleukin-1 β[J]. J Neuroinflammation, 2012, 9: 280.
[10]
Madadi A, Wolfart J, Lange F, et al. Correlation between Kir4.1 expression and barium-sensitive currents in rat and human glioma cell lines[J]. Neurosci Lett, 2021, 741: 135481.
[11]
Olsen ML, Sontheimer H. Functional implications for Kir4.1 channels in glial biology: from K+ buffering to cell differentiation[J]. J Neurochem, 2008, 107(3): 589-601.
[12]
Lin ZX. Glioma-related edema: new insight into molecular mechanisms and their clinical implications[J]. Chin J Cancer, 2013, 32(1): 49-52.
[13]
Tham DK, Moukhles H. Regulation of Kir4.1 and AQP4 expression and stability at the basolateral domain of epithelial MDCK cells by the extracellular matrix[J]. Am J Physiol Renal Physiol, 2011, 301(2): F396-F409.
[14]
Warth A, Mittelbronn M, Wolburg H. Redistribution of the water channel protein aquaporin-4 and the K+ channel protein Kir4.1 differs in low- and high-grade human brain tumors[J]. Acta Neuropathol, 2005, 109(4): 418-426.
[15]
Binder DK, Nagelhus EA, Ottersen OP. Aquaporin-4 and epilepsy[J]. Glia, 2012, 60(8): 1203-1214.
[16]
Hubbard JA, Binder DK. Water channels - sciencedirect[M]//Hubbard JA, Binder DK. Astrocytes and Epilepsy. Pittsburgh: Academic Press, 2016: 171-195.
[17]
费晓炜,徐如祥,魏明海, 等. 局灶性脑低温处理对大鼠创伤性脑损伤模型的保护作用[J]. 中华神经创伤外科电子杂志, 2019, 5(2): 101-105.
[18]
Hubbard JA, Szu JI, Yonan JM, et al. Regulation of astrocyte glutamate transporter-1 (GLT1) and aquaporin-4 (AQP4) expression in a model of epilepsy[J]. Exp Neurol, 2016, 283(Pt A): 85-96.
[19]
Lei S, He Y, Zhu Z, et al. Inhibition of NMDA receptors downregulates astrocytic AQP4 to suppress seizures[J]. Cell Mol Neurobiol, 2020, 40(8): 1283-1295.
[20]
Heuser K, Nagelhus EA, Taubøll E, et al. Variants of the genes encoding AQP4 and Kir4.1 are associated with subgroups of patients with temporal lobe epilepsy[J]. Epilepsy Res, 2010, 88(1): 55-64.
[1] 王子杨, 杨文利, 李栋军, 陈伟, 赵琦, 李逸丰, 崔蕊, 沈琳, 刘倩, 魏串串. 高频线阵探头对眼球壁的临床观察[J/OL]. 中华医学超声杂志(电子版), 2024, 21(06): 580-584.
[2] 邓呈亮, 陈君哲, 章一新. 继发性肢体淋巴水肿的外科整合治疗[J/OL]. 中华损伤与修复杂志(电子版), 2024, 19(03): 185-191.
[3] 黄福, 王黔, 金相任, 唐云川. VEGFR2、miR-27a-5p在胃癌组织中的表达与临床病理参数及预后的关系研究[J/OL]. 中华普外科手术学杂志(电子版), 2024, 18(05): 558-561.
[4] 祝炜安, 林华慧, 吴建杰, 黄炯煅, 吴婷婷, 赖文杰. RDM1通过CDK4促进前列腺癌细胞进展的研究[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(06): 618-625.
[5] 胡思平, 熊性宇, 徐航, 杨璐. 衰老相关分泌表型因子在前列腺癌发生发展中的作用机制[J/OL]. 中华腔镜泌尿外科杂志(电子版), 2024, 18(05): 425-434.
[6] 赵蒙蒙, 黄洁, 余荣环, 王葆青. 过表达小GTP酶Rab32抑制非小细胞肺癌细胞侵袭性生长[J/OL]. 中华肺部疾病杂志(电子版), 2024, 17(04): 512-518.
[7] 黄程鑫, 陈莉, 刘伊楚, 王水良, 赖晓凤. OPA1 在乳腺癌组织的表达特征及在ER阳性乳腺癌细胞中的生物学功能研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(05): 275-284.
[8] 曾聿理, 雷发容, 肖慧, 邱德亮, 谢静, 吴寻. 氯普鲁卡因通过调控circRNA-ZKSCAN1表达抑制肝癌Huh-7细胞体外生长和转移的研究[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(04): 220-228.
[9] 李彦浇, 梁雷, 金钫, 王智伟. 银杏内酯B通过调控miR-24-3p对人牙周膜干细胞增殖、成骨分化的影响[J/OL]. 中华细胞与干细胞杂志(电子版), 2024, 14(04): 229-235.
[10] 杨兴业, 彭旭云, 曾倩, 梁伟铖, 肖翠翠, 郑俊, 姚嘉. LMO7通过靶向铁死亡促进肝细胞癌生长[J/OL]. 中华肝脏外科手术学电子杂志, 2024, 13(03): 370-376.
[11] 崔精, 鲍一帆, 沈晓明, 杨增辉, 高森, 鲍传庆. 结直肠癌中circMFSD12对肿瘤细胞功能及5-FU敏感性的调控[J/OL]. 中华结直肠疾病电子杂志, 2024, 13(04): 294-302.
[12] 王旭颖, 王玮, 李贵刚. 把握内眼术后角膜水肿行角膜内皮移植术的时机[J/OL]. 中华眼科医学杂志(电子版), 2024, 14(04): 193-199.
[13] 张小凤, 孙晓琴, 黄军, 冀涵页, 杨辉, 侯智, 张春青. 标准前颞叶切除术治疗药物难治性癫痫[J/OL]. 中华神经创伤外科电子杂志, 2024, 10(03): 189-192.
[14] 王国强, 张纲, 唐建坡, 张玉国, 杨永江. LINC00839 调节miR-17-5p/WEE1 轴对结直肠癌细胞增殖、凋亡和迁移的影响[J/OL]. 中华消化病与影像杂志(电子版), 2024, 14(06): 491-499.
[15] 靳英, 付小霞, 陈美茹, 袁璐, 郝力瑶. CD147调控MAPK信号通路对结肠癌细胞增殖和凋亡的影响及机制研究[J/OL]. 中华临床医师杂志(电子版), 2024, 18(05): 474-480.
阅读次数
全文


摘要