Department of Human Anatomy, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430070, China.
Biomolecules. 2024 Mar 6;14(3):314. doi: 10.3390/biom14030314.
Gliomas, the most prevalent and lethal form of brain cancer, are known to exhibit metabolic alterations that facilitate tumor growth, invasion, and resistance to therapies. Peroxisomes, essential organelles responsible for fatty acid oxidation and reactive oxygen species (ROS) homeostasis, rely on the receptor PEX5 for the import of metabolic enzymes into their matrix. However, the prognostic significance of peroxisomal enzymes for glioma patients remains unclear. In this study, we elucidate that PEX5 is indispensable for the cell growth, migration, and invasion of glioma cells. We establish a robust prognosis model based on the expression of peroxisomal enzymes, whose localization relies on PEX5. This PEX5-dependent signature not only serves as a robust prognosis model capable of accurately predicting outcomes for glioma patients, but also effectively distinguishes several clinicopathological features, including the grade, isocitrate dehydrogenase () mutation, and 1p19q codeletion status. Furthermore, we developed a nomogram that integrates the prognostic model with other clinicopathological factors, demonstrating highly accurate performance in estimating patient survival. Patients classified into the high-risk group based on our prognostic model exhibited an immunosuppressive microenvironment. Finally, our validation reveals that the elevated expression of , an antioxidant enzyme within the signature, promotes the cell growth and migration of glioma cells, with this effect dependent on the peroxisomal targeting signal recognized by PEX5. These findings identify the PEX5-dependent signature as a promising prognostic tool for gliomas.
神经胶质瘤是最常见和最致命的脑癌形式，已知其表现出代谢改变，促进肿瘤生长、侵袭和对治疗的抵抗。过氧化物酶体是负责脂肪酸氧化和活性氧（ROS）平衡的重要细胞器，依赖受体 PEX5 将代谢酶导入其基质。然而，过氧化物酶体酶对神经胶质瘤患者的预后意义尚不清楚。在这项研究中，我们阐明了 PEX5 对于神经胶质瘤细胞的生长、迁移和侵袭是必不可少的。我们建立了一个基于过氧化物酶体酶表达的稳健预后模型，其定位依赖于 PEX5。这个依赖于 PEX5 的特征不仅是一个稳健的预后模型，能够准确预测神经胶质瘤患者的预后，而且还能有效地区分几个临床病理特征，包括分级、异柠檬酸脱氢酶（IDH）突变和 1p19q 缺失状态。此外，我们开发了一个列线图，将预后模型与其他临床病理因素相结合，在估计患者生存方面表现出高度准确的性能。根据我们的预后模型，被分类为高危组的患者表现出免疫抑制的微环境。最后，我们的验证表明，该特征中抗氧化酶的表达升高，促进了神经胶质瘤细胞的生长和迁移，这种作用依赖于 PEX5 识别的过氧化物酶体靶向信号。这些发现确定了依赖于 PEX5 的特征是神经胶质瘤有前途的预后工具。
