Liu Zhichun, Liu Junhui, Chen Zhibiao, Zhu Xiaonan, Ding Rui, Huang Shulan, Xu Haitao
Department of Neurosurgery, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Biomedicines. 2024 Nov 11;12(11):2579. doi: 10.3390/biomedicines12112579.
Chloride Intracellular Channel 4 () plays a versatile role in cellular functions beyond its role in primary chloride ion transport. Notably, many studies found an association between expression and cancers. However, the correlation between and glioma remains to be uncovered.
A total of 3162 samples from nine public datasets were analyzed to reveal the relationship between expression and glioma malignancy or prognosis. Immunohistochemistry (IHC) staining was performed to examine the results in an in-house cohort. A nomogram model was constructed to predict the prognosis. Functional enrichment analysis was employed to find -associated differentially expressed genes in glioma. Immune infiltration analysis, correlation analysis, and IHC staining were employed, aiming to examine the correlation between expression, immune cell infiltration, and ECM (extracellular matrix)-related genes.
The expression level of was correlated with the malignancy of glioma and the prognosis of patients. More aggressive gliomas and mesenchymal GBM are associated with a high expression of . Gliomas with IDH mutation or 1p19q codeletion express a low level of , and a high expression of correlates with poor prognosis. The nomogram model shows a good predictive performance. The DEGs (differentially expressed genes) in gliomas with high and low expression are enriched in extracellular matrix and immune functions. On the one hand, gliomas with high expression have a greater presence of macrophages, neutrophils, and eosinophils; on the other hand, a high expression in gliomas is positively associated with ECM-related genes.
Compared to glioma cells with low expression, gliomas with high expression exhibit greater malignancy and poorer prognosis. Our findings indicate that a high level of correlates with high expression of ECM-related genes and the infiltration of macrophages, neutrophils, and eosinophils within glioma tissues.
氯离子细胞内通道4（CLIC4）在细胞功能中发挥着多种作用，超出了其在初级氯离子转运中的作用。值得注意的是，许多研究发现CLIC4表达与癌症之间存在关联。然而，CLIC4与胶质瘤之间的相关性仍有待揭示。
分析来自九个公共数据集的总共3162个样本，以揭示CLIC4表达与胶质瘤恶性程度或预后之间的关系。进行免疫组织化学（IHC）染色以在内部队列中检验结果。构建列线图模型以预测预后。采用功能富集分析来寻找胶质瘤中与CLIC4相关的差异表达基因。采用免疫浸润分析、相关性分析和IHC染色，旨在检验CLIC4表达、免疫细胞浸润和细胞外基质（ECM）相关基因之间的相关性。
CLIC4的表达水平与胶质瘤的恶性程度和患者的预后相关。侵袭性更强的胶质瘤和间充质型胶质母细胞瘤与CLIC4的高表达相关。具有异柠檬酸脱氢酶（IDH）突变或1p19q共缺失的胶质瘤表达水平较低，而CLIC4的高表达与预后不良相关。列线图模型显示出良好的预测性能。CLIC4高表达和低表达的胶质瘤中的差异表达基因（DEGs）在细胞外基质和免疫功能方面富集。一方面，CLIC4高表达的胶质瘤中巨噬细胞、中性粒细胞和嗜酸性粒细胞的存在更多；另一方面，胶质瘤中CLIC4的高表达与ECM相关基因呈正相关。
与CLIC4低表达相比，CLIC4高表达的胶质瘤表现出更高的恶性程度和更差的预后。我们的研究结果表明，高水平的CLIC4与胶质瘤组织中ECM相关基因的高表达以及巨噬细胞、中性粒细胞和嗜酸性粒细胞的浸润相关。
