PANK1 在脑胶质瘤中的表达及预后作用。
Expression and Prognostic Role of PANK1 in Glioma.
机构信息
Department of Geriatrics, Renmin Hospital of Wuhan University, Wuchang District, Wuhan, 430060, China.
出版信息
Comb Chem High Throughput Screen. 2024;27(5):715-724. doi: 10.2174/1386207326666230502103726.
BACKGROUND
Malignant gliomas are the most common type of primary malignant brain tumors. Pantothenate kinase 1 (PANK1) mRNA is highly expressed in several metabolic processes, implying that PANK1 plays a potential role in metabolic programming in cancers. However, the role of PANK1 in glioma has not been fully explored.
METHODS
Public datasets (The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Gravendeel and Rembrandt) and validation cohort were used to explore the expression of PANK1 in glioma tissues. Kaplan-Meier and Cox regression analyses were used to explore the relationship between PANK1 and prognosis in glioma. Cell proliferation and invasion were determined using Cell Counting Kit-8 (CCK8) and transwell invasion assays.
RESULTS
Analysis using the four public datasets and the validation cohort showed that PANK1 expression was significantly downregulated in glioma tissues compared with non-tumor tissues (P<0.01). PANK1 expression was negatively correlated with World Health Organization (WHO) grade, 1p/19q non-codeletion and isocitric dehydrogenase 1/2 (IDH1/2) wildtype. Furthermore, high expression of PANK1 was correlated with significantly better prognosis of glioma patients compared to patients with low expression of PANK1 (all P<0.01 in the four datasets). Besides, both lower-grade glioma (LGG) and glioblastoma multiform (GBM) patients with high expression of PANK1 had a significantly better prognosis than those with low expression of PANK1 in TCGA, Gravendeel and Rembrandt datasets (all P <0.01). Multivariate Cox regression analysis revealed that low PANK1 expression was an independent risk factor associated with a worse prognosis of glioma patients. Moreover, overexpression of PANK1 significantly inhibited the proliferation and invasion of U87 and U251 cells.
CONCLUSION
PANK1 expression is downregulated in glioma tissues and is a novel prognostic biomarker in glioma patients.
背景
恶性神经胶质瘤是最常见的原发性恶性脑肿瘤。泛酸激酶 1（PANK1）mRNA 在几种代谢过程中高度表达，这意味着 PANK1 在癌症的代谢编程中发挥潜在作用。然而，PANK1 在神经胶质瘤中的作用尚未得到充分探索。
方法
使用公共数据集（癌症基因组图谱（TCGA）、中国神经胶质瘤基因组图谱（CGGA）、Gravendeel 和 Rembrandt）和验证队列来研究 PANK1 在神经胶质瘤组织中的表达。Kaplan-Meier 和 Cox 回归分析用于研究 PANK1 与神经胶质瘤预后的关系。使用细胞计数试剂盒-8（CCK8）和 Transwell 侵袭实验来确定细胞增殖和侵袭。
结果
使用四个公共数据集和验证队列的分析表明，与非肿瘤组织相比，神经胶质瘤组织中 PANK1 的表达显著下调（P<0.01）。PANK1 的表达与世界卫生组织（WHO）分级、1p/19q 非缺失和异柠檬酸脱氢酶 1/2（IDH1/2）野生型呈负相关。此外，与 PANK1 低表达的患者相比，PANK1 高表达的神经胶质瘤患者的预后明显更好（四个数据集均 P<0.01）。此外，在 TCGA、Gravendeel 和 Rembrandt 数据集中，PANK1 高表达的低级别神经胶质瘤（LGG）和多形性胶质母细胞瘤（GBM）患者的预后明显优于 PANK1 低表达的患者（均 P<0.01）。多变量 Cox 回归分析显示，PANK1 低表达是与神经胶质瘤患者预后不良相关的独立危险因素。此外，过表达 PANK1 显著抑制了 U87 和 U251 细胞的增殖和侵袭。
结论
PANK1 在神经胶质瘤组织中表达下调，是神经胶质瘤患者的一种新的预后生物标志物。
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