Kaushal Prashant, Zhu Junle, Wan Zhiping, Chen Huairui, Ye Jingliang, Luo Chun
Department of Neurosurgery, Tongji Hospital, School of Medicine, Tongji University, Shanghai, China.
Neuromolecular Med. 2023 Mar;25(1):102-119. doi: 10.1007/s12017-022-08719-w. Epub 2022 Jul 2.
Glioblastoma (GBM) is the most malignant and aggressive primary brain tumor and is highly resistant to current therapeutic strategies. Previous studies have demonstrated that reactive oxygen species (ROS) play an important role in the regulation of signal transduction and immunosuppressive environment in GBM. To further study the role of ROS in prognosis, tumor micro-environment (TME) and immunotherapeutic response in GBM, an ROS-related nine-gene signature was constructed using the Lasso-Cox regression method and validated using three other datasets in our research, based on the hallmark ROS-pathway-related gene sets and the Cancer Genome Atlas GBM dataset. Differences in prognosis, TME scores, immune cell infiltration, immune checkpoint expression levels, and drug sensitivity between high-risk and low-risk subgroups were analyzed using R software. Collectively, our research uncovered a novel ROS-related prognostic model for primary GBM, which could prove to be a potential tool for clinical diagnosis of GBM, and help assess the immune and molecular characteristics of ROS in the tumorigenesis and immunosuppression of GBM. Our research also revealed that the expressions of ROS-related genes-HSPB1, LSP1, and PTX3-were closely related to the cell markers of tumor-associated macrophages (TAMs) and M2 macrophages validated by quantitative RT-PCR, suggesting them could be potential targets of immunotherapy for GBM.
胶质母细胞瘤（GBM）是最恶性且侵袭性最强的原发性脑肿瘤，对当前的治疗策略具有高度抗性。先前的研究表明，活性氧（ROS）在GBM的信号转导调控和免疫抑制环境中发挥着重要作用。为了进一步研究ROS在GBM预后、肿瘤微环境（TME）和免疫治疗反应中的作用，我们基于标志性ROS通路相关基因集和癌症基因组图谱GBM数据集，使用套索-考克斯回归方法构建了一个与ROS相关的九基因特征，并在我们的研究中使用其他三个数据集进行了验证。使用R软件分析了高风险和低风险亚组之间在预后、TME评分、免疫细胞浸润、免疫检查点表达水平和药物敏感性方面的差异。总体而言，我们的研究发现了一种用于原发性GBM的新型ROS相关预后模型，这可能成为GBM临床诊断的潜在工具，并有助于评估ROS在GBM肿瘤发生和免疫抑制中的免疫和分子特征。我们的研究还表明，通过定量逆转录-聚合酶链反应验证，与ROS相关的基因HSPB1、LSP1和PTX3的表达与肿瘤相关巨噬细胞（TAM）和M2巨噬细胞的细胞标志物密切相关，表明它们可能是GBM免疫治疗的潜在靶点。
