Department of Pediatrics, Zhongnan Hospital of Wuhan University, Wuhan, China.
J Clin Lab Anal. 2023 Apr;37(8):e24892. doi: 10.1002/jcla.24892. Epub 2023 May 9.
Among the brain and the other central nervous system, gliomas are the most prevalent malignant primary tumors. Adenylate kinase 2 (AK2) is generally thought to be crucial for energy metabolism and signal transduction. Several disorders are correlated with its aberrant expression. However, it is unclear what functions AK2 might have in gliomas.
We investigated the relationship between AK2 expression and clinicopathological features of glioma patients using information obtained from public databases and patient tissue microarrays. AK2 knockdown glioma cell lines were constructed to explore how AK2 affects glioma progress. The association between AK2 and the immune microenvironment in gliomas was evaluated by multiple methods.
AK2 expression was higher in glioma samples than in normal brain tissues. Older patients and those with higher-grade, IDH-wildtype, 1p/19q codeletion-free, and MGMT-unmethylated tumors had higher levels of AK2 expression, linking to poor outcomes. Thus, gliomas with high AK2 expression have a worse prognosis. GO and KEGG analyses demonstrated that AK2 was relevant to cell division and DNA replication. Downregulation of AK2 suppresses cell proliferation, migration, and colony formation of glioma cell lines in vitro. AK2 expression was positively connected to the inhibitory immune checkpoints, also correlating with immune infiltration degree.
In this study, AK2 may be a potential biological target for more precise molecular therapy of gliomas, since its high expression is associated with worse outcomes and a more malignant immune microenvironment.
在大脑和其他中枢神经系统中,神经胶质瘤是最常见的恶性原发性肿瘤。腺苷酸激酶 2(AK2)通常被认为对能量代谢和信号转导至关重要。几种疾病与其异常表达相关。然而,AK2 在神经胶质瘤中的功能尚不清楚。
我们使用从公共数据库和患者组织微阵列中获得的信息,研究了 AK2 表达与神经胶质瘤患者临床病理特征之间的关系。构建 AK2 敲低神经胶质瘤细胞系,以探讨 AK2 如何影响神经胶质瘤的进展。通过多种方法评估 AK2 与神经胶质瘤免疫微环境之间的关系。
与正常脑组织相比,神经胶质瘤样本中 AK2 的表达更高。年龄较大的患者以及 IDH 野生型、1p/19q 无缺失、MGMT 未甲基化的高级别肿瘤患者 AK2 表达水平更高,与不良预后相关。因此,高 AK2 表达的神经胶质瘤预后更差。GO 和 KEGG 分析表明 AK2 与细胞分裂和 DNA 复制有关。AK2 下调抑制了神经胶质瘤细胞系在体外的增殖、迁移和集落形成。AK2 表达与抑制性免疫检查点呈正相关,也与免疫浸润程度相关。
在这项研究中,AK2 可能是神经胶质瘤更精确的分子治疗的潜在生物靶点,因为其高表达与不良预后和更恶性的免疫微环境有关。