Department of Neurosurgery, Beijing Jishuitan Hospital, Xicheng District, Beijing, China.
Department of Neurosurgery, Beijing Jishuitan Hospital, Xicheng District, Beijing, China.
World Neurosurg. 2023 Jul;175:e713-e722. doi: 10.1016/j.wneu.2023.04.010. Epub 2023 Apr 8.
Aquaporin-4 (AQP4) is a significant factor in transcellular and transepithelial water movement, and abnormal expression of AQP4 has been detected in many types of tumors. The purpose of this study was to explore its role in low-grade gliomas (LGG) using freely available online bioinformatics tools.
OncoLnc database was used to analyze Cox coefficients and compare AQP4 expression between various types of tumors; Tumor Immune Estimation Resource database and Gene Expression Profiling Interactive Analysis were used to compare gene expression between LGG and normal tissues; University of California Santa Cruz Xena browser generated Kaplan-Meier survival curves in the LGG cohort in The Cancer Genome Atlas and subgroups; LinkedOmics database screened the most relevant genes based on Pearson correlation coefficient; Gene Ontology Biological Process and Kyoto Encyclopedia of Genes and Genomes enrichment analysis were performed through gene set enrichment analysis to explore possible molecular mechanisms.
LGG had higher AQP4 expression compared with normal tissues and ranked first among 21 different types of cancer (P < 0.05). The oligodendroglioma group had the lowest AQP4 expression and the longest overall survival (OS) (P < 0.05). LGG with astrocytoma, isocitrate dehydrogenase mutation, or 1p/19q codeletion had lower AQP4 expression and longer OS (P < 0.001). LGG with lower AQP4 expression, without 1p/19q codeletion, without chemotherapy, and with or without radiation therapy had longer OS (P < 0.05). AQP4 and coexpressed genes were involved in complex biological processes in LGG, including regulation of neurotransmitter level, peroxisome proliferator-activated receptor signaling pathway, cell adhesion molecules, and others.
AQP4 is a prognostic marker in LGG and its subgroups. Patients with lower AQP4 expression may have longer OS.
水通道蛋白-4（AQP4）是细胞间和跨上皮水运动的重要因素，AQP4 的异常表达已在许多类型的肿瘤中被检测到。本研究旨在使用免费的在线生物信息学工具探讨其在低级别胶质瘤（LGG）中的作用。
OncoLnc 数据库用于分析 Cox 系数并比较各种类型肿瘤之间的 AQP4 表达；肿瘤免疫估计资源数据库和基因表达谱交互式分析用于比较 LGG 和正常组织之间的基因表达；加州大学圣克鲁斯 Xena 浏览器在癌症基因组图谱和亚组中的 LGG 队列中生成 Kaplan-Meier 生存曲线；LinkedOmics 数据库根据 Pearson 相关系数筛选最相关的基因；通过基因集富集分析进行基因本体论生物过程和京都基因与基因组百科全书富集分析，以探讨可能的分子机制。
与正常组织相比，LGG 具有更高的 AQP4 表达，在 21 种不同类型的癌症中排名第一（P < 0.05）。少突胶质细胞瘤组 AQP4 表达最低，总生存期（OS）最长（P < 0.05）。具有星形细胞瘤、异柠檬酸脱氢酶突变或 1p/19q 联合缺失的 LGG 具有较低的 AQP4 表达和更长的 OS（P < 0.001）。具有较低 AQP4 表达、无 1p/19q 联合缺失、无化疗且无或有放疗的 LGG 具有更长的 OS（P < 0.05）。AQP4 和共表达基因参与 LGG 中的复杂生物学过程，包括神经递质水平的调节、过氧化物酶体增殖物激活受体信号通路、细胞黏附分子等。
AQP4 是 LGG 及其亚组的预后标志物。具有较低 AQP4 表达的患者可能具有更长的 OS。
