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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]. 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]. 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
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