Guo Yangyang, Bao Jingxia, Lin Danfeng, Hong Kai, Cen Kenan, Sun Jie, Wang Zhepei, Wu Zhixuan
Department of Neurosurgery, The First Affiliated Hospital of Ningbo University, Haishu District, Ningbo, 315010, Zhejiang, People's Republic of China.
Department of Breast Surgery, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang, People's Republic of China.
Heliyon. 2023 Sep 14;9(9):e20178. doi: 10.1016/j.heliyon.2023.e20178. eCollection 2023 Sep.
Recently, studies have shown that immune checkpoint-related genes (ICGs) are instrumental in maintaining immune homeostasis and can be regarded as potential therapeutic targets. However, the prognostic applications of ICGs require further elucidation in low-grade glioma (LGG) cases. In the present study, a unique prognostic gene signature in LGG has been identified and validated as well based on ICGs as a means of facilitating clinical decision-making. The RNA-seq data as well as corresponding clinical data of LGG samples have been retrieved utilizing the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. ICG-defined non-negative matrix factorization (NMF) clustering was performed to categorize patients with LGG into two molecular subtypes with different prognoses, clinical traits, and immune microenvironments. In the TCGA database, a signature integrating 8 genes has been developed utilizing the LASSO Cox method and validated in the GEO database. The signature developed is superior to other well-recognized signatures in terms of predicting the survival probability of patients with LGG. This 8-gene signature was then subsequently applied to categorize patients into high- and low-risk groups, and differences between them in terms of gene alteration frequency were observed. There were remarkable variations in IDH1 (91% and 64%) across low-as well as high-risk groups. Additionally, various analyses like function enrichment, tumor immune microenvironment, and chemotherapy drug sensitivity revealed significant variations across high- and low-risk populations. Overall, this 8-gene signature may function as a useful tool for prognosis and immunotherapy outcome predictions among LGG patients.
最近的研究表明,免疫检查点相关基因(ICGs)在维持免疫稳态中发挥着重要作用,可被视为潜在的治疗靶点。然而,ICGs在低级别胶质瘤(LGG)病例中的预后应用仍需进一步阐明。在本研究中,基于ICGs识别并验证了一种独特的LGG预后基因特征,以促进临床决策。利用癌症基因组图谱(TCGA)和基因表达综合数据库(GEO)检索了LGG样本的RNA测序数据及相应的临床数据。进行了ICG定义的非负矩阵分解(NMF)聚类,将LGG患者分为具有不同预后、临床特征和免疫微环境的两种分子亚型。在TCGA数据库中,利用LASSO Cox方法开发了一个整合8个基因的特征,并在GEO数据库中进行了验证。所开发的特征在预测LGG患者的生存概率方面优于其他公认的特征。然后将这个8基因特征应用于将患者分为高风险和低风险组,并观察了两组之间基因改变频率的差异。低风险组和高风险组的IDH1(分别为91%和64%)存在显著差异。此外,功能富集、肿瘤免疫微环境和化疗药物敏感性等各种分析显示,高风险和低风险人群之间存在显著差异。总体而言,这个8基因特征可能是预测LGG患者预后和免疫治疗结果的有用工具。