Lin Liangbin, Yu Hui, Xie Xuelu, Lei Qingqiang, Chen Xuerui, Su Xu, Wang Xiuxuan, Zhang Sunfu, Yang Wenyong
Department of Neurosurgery and Urology, Medical Research Center, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University, The Second Chengdu Hospital Affiliated to Chongqing Medical University Chengdu 610014, Sichuan, The People's Republic of China.
Obesity and Metabolism Medicine-Engineering Integration Laboratory, Department of General Surgery, The Third People's Hospital of Chengdu, The Affiliated Hospital of Southwest Jiaotong University Chengdu 610031, The People's Republic of China.
Am J Cancer Res. 2024 Jun 15;14(6):2731-2754. doi: 10.62347/GIGO3446. eCollection 2024.
Heterogeneity at biological and transcriptomic levels poses a challenge in defining and typing low-grade glioma (LGG), leading to a critical need for specific molecular signatures to enhance diagnosis, therapy, and prognostic evaluation of LGG. This study focused on fatty acid metabolism (FAM) related genes and prognostic features to investigate the mechanisms and treatment strategies for LGG cell metastasis and invasion. By screening 158 FAM-related genes and clustering 512 LGG samples into two subtypes (C1 and C2), differential gene expression analysis and functional enrichment were performed. The immune cell scores and prognosis were compared between the two subtypes, with C1 showing poorer outcomes and higher immune scores. A four-gene signature (PHEX, SHANK2, HOPX, and LGALS1) was identified and validated across different datasets, demonstrating a stable predictive effect. Cellular experiments confirmed the roles of LGALS1 and HOPX in promoting tumor cell proliferation, migration, and invasion, while SHANK2 exhibited a suppressive effect. This four-gene signature based on FAM-related genes offers valuable insights for understanding the pathogenesis and clinical management of LGG.
生物学和转录组水平的异质性给低级别胶质瘤(LGG)的定义和分型带来了挑战,这使得迫切需要特定的分子特征来加强LGG的诊断、治疗和预后评估。本研究聚焦于脂肪酸代谢(FAM)相关基因和预后特征,以探究LGG细胞转移和侵袭的机制及治疗策略。通过筛选158个FAM相关基因并将512个LGG样本聚类为两个亚型(C1和C2),进行了差异基因表达分析和功能富集分析。比较了两个亚型之间的免疫细胞评分和预后,C1显示出较差的结果和更高的免疫评分。鉴定了一个四基因特征(PHEX、SHANK2、HOPX和LGALS1)并在不同数据集中进行了验证,显示出稳定的预测效果。细胞实验证实了LGALS1和HOPX在促进肿瘤细胞增殖、迁移和侵袭中的作用,而SHANK2表现出抑制作用。这种基于FAM相关基因的四基因特征为理解LGG的发病机制和临床管理提供了有价值的见解。