El-Arabey Amr Ahmed, Alkhalil Samia S, AlAfaleq Nouf Omar, Al-Shouli Sawsan, Mohamed Samah Saif Eldin M, Al-Shouli Samia T, Abdalla Mohnad
Applied College, King Khalid University, P. O. Box 9004, 61413, Abha, Saudi Arabia.
Center of Bee Research and Its Products, King Khalid University, P. O. Box 9004, 61413, Abha, Saudi Arabia.
J Mol Neurosci. 2025 Mar 18;75(2):37. doi: 10.1007/s12031-025-02323-w.
Low-grade gliomas (LGG) are malignant brain tumors that arise from the brain's support cells (glial cells). LGG are the most common kind of central nervous system tumors in children and adolescents, accounting for around half of all cases. Tumor Protein p53 (TP53) regulates or promotes DNA damage and repair via a variety of cell cycle, apoptosis, and genomic stability pathways. However, the clinical role of TP53 status in LGG patients is still unknown. Hence, we analyzed clinical data from the Cancer Genomic Atlas (TCGA) of LGG patients to see if TP53 status affects clinical outcomes, molecular signatures of chemokines and microRNAs, and immune cell infiltrations within the tumor's microenvironment of LGG patients. According to our findings, the most common phenotype in LGG patients is wild-type TP53, which is related to poor clinical outcomes and the expression of Chemokine ligand 14 (CXCL14) in many clinical parameters such as age, gender, stage, race, and purity. Besides, in LGG patients, wild-type TP53 controls prognostic microRNAs such as has-miR-10a-3p and has-miR-155-5p. Furthermore, through activating GATA Binding Protein 3 (GATA3) and decreasing Fatty Acid Synthase (FASN), wild-type TP53 orchestrates M1 macrophage and CD8 T cell infiltration, as well as the formation of brown adipose tissue and decreased white adipose tissue. In this regard, the TP53-CXCL14-GATA3 axis has the potential to predict poor clinical outcomes in patients with wild-type TP53 LGG.
低级别胶质瘤(LGG)是起源于脑支持细胞(神经胶质细胞)的恶性脑肿瘤。LGG是儿童和青少年中最常见的中枢神经系统肿瘤类型,约占所有病例的一半。肿瘤蛋白p53(TP53)通过多种细胞周期、凋亡和基因组稳定性途径调节或促进DNA损伤与修复。然而,TP53状态在LGG患者中的临床作用仍不明确。因此,我们分析了来自癌症基因组图谱(TCGA)的LGG患者临床数据,以探究TP53状态是否会影响临床结局、趋化因子和微小RNA的分子特征以及LGG患者肿瘤微环境中的免疫细胞浸润情况。根据我们的研究结果,LGG患者中最常见的表型是野生型TP53,其在年龄、性别、分期、种族和肿瘤纯度等许多临床参数方面与较差的临床结局及趋化因子配体14(CXCL14)的表达相关。此外,在LGG患者中,野生型TP53控制着诸如has-miR-10a-3p和has-miR-155-5p等预后微小RNA。再者,通过激活GATA结合蛋白3(GATA3)并降低脂肪酸合酶(FASN),野生型TP53协调M1巨噬细胞和CD8 T细胞浸润,以及棕色脂肪组织的形成和白色脂肪组织的减少。在这方面,TP53-CXCL14-GATA3轴有可能预测野生型TP53 LGG患者的不良临床结局。