Liu Zaoqu, Xu Yudi, Wang Yuhui, Weng Siyuan, Xu Hui, Ren Yuqing, Guo Chunguang, Liu Long, Zhang Zhenyu, Han Xinwei
Department of Interventional Radiology The First Affiliated Hospital of Zhengzhou University Zhengzhou China.
Interventional Institute of Zhengzhou University Zhengzhou China.
Imeta. 2023 Jul 16;2(3):e127. doi: 10.1002/imt2.127. eCollection 2023 Aug.
The immune system is an interacting network of plentiful molecules that could better characterize the relationship between immunity and cancer. This study aims to investigate the behavioral patterns of immune-related interaction perturbation networks in glioblastoma. An immune-related interaction-perturbation framework was introduced to characterize four heterogeneous subtypes using RNA-seq data of TCGA/CGGA glioblastoma tissues and GTEx normal brain tissues. The stability and robustness of the four subtypes were validated in public datasets and our in-house cohort. In the four subtypes, C1 was an inflammatory subtype with high immune infiltration, low tumor purity, and potential response to immunotherapy; C2, an invasive subtype, was featured with dismal prognosis, telomerase reverse transcriptase promoter mutations, moderate levels of immunity, and stromal constituents, as well as sensitivity to receptor tyrosine kinase signaling inhibitors; C3 was a proliferative subtype with high tumor purity, immune-desert microenvironment, sensitivity to phosphatidylinositol 3'-kinase signaling inhibitor and DNA replication inhibitors, and potential resistance to immunotherapy; C4, a synaptogenesis subtype with the best prognosis, exhibited high synaptogenesis-related gene expression, prevalent isocitrate dehydrogenase mutations, and potential sensitivity to radiotherapy and chemotherapy. Overall, this study provided an attractive platform from the perspective of immune-related interaction perturbation networks, which might advance the tailored management of glioblastoma.
免疫系统是一个由丰富分子组成的相互作用网络，它能更好地描述免疫与癌症之间的关系。本研究旨在探讨胶质母细胞瘤中免疫相关相互作用扰动网络的行为模式。引入了一个免疫相关相互作用扰动框架，利用TCGA/CGGA胶质母细胞瘤组织和GTEx正常脑组织的RNA-seq数据来表征四种异质性亚型。这四种亚型的稳定性和稳健性在公共数据集和我们的内部队列中得到了验证。在这四种亚型中，C1是一种炎症亚型，具有高免疫浸润、低肿瘤纯度以及对免疫治疗的潜在反应；C2是一种侵袭性亚型，其特征是预后不良、端粒酶逆转录酶启动子突变、中等水平的免疫和基质成分，以及对受体酪氨酸激酶信号抑制剂敏感；C3是一种增殖性亚型，具有高肿瘤纯度、免疫荒漠微环境、对磷脂酰肌醇3'-激酶信号抑制剂和DNA复制抑制剂敏感，以及对免疫治疗有潜在抗性；C4是一种突触发生亚型，预后最佳，表现出高突触发生相关基因表达、普遍的异柠檬酸脱氢酶突变，以及对放疗和化疗的潜在敏感性。总体而言，本研究从免疫相关相互作用扰动网络的角度提供了一个有吸引力的平台，这可能会推动胶质母细胞瘤的个体化管理。
