Department of Neurology, Shenzhen Nanshan People's Hospital and the 6th Affiliated Hospital of Shenzhen University Health Science Center, Shenzhen, 518052, Guangdong, China.
State Key Laboratory of Oncogenes and Related Genes, School of Medicine, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, Shanghai Jiao Tong University, Shanghai, 200127, China.
Hum Cell. 2022 Nov;35(6):1976-1992. doi: 10.1007/s13577-022-00791-5. Epub 2022 Sep 21.
Gliomas are the most common primary brain tumors and are highly malignant with a poor prognosis. Pyroptosis, an inflammatory form of programmed cell death, promotes the inflammatory cell death of cancer. Studies have demonstrated that pyroptosis can promote the inflammatory cell death (ICD) of cancer, thus affecting the prognosis of cancer patients. Therefore, genes that control pyroptosis could be a promising candidate bio-indicator in tumor therapy. The function of pyroptosis-related genes (PRGs) in gliomas was investigated based on the Chinese Glioma Genome Atlas (CGGA), the Cancer Genome Atlas (TCGA) and the Repository of Molecular Brain Neoplasia Data (Rembrandt) databases. In this study, using the non-negative matrix factorization (NMF) clustering method, 26 PRGs from the RNA sequencing data were divided into two subgroups. The LASSO and Cox regression was used to develop a 4-gene (BAX, Caspase-4, Caspase-8, PLCG1) risk signature, and all glioma patients in the CGGA, TCGA and Rembrandt cohorts were divided into low- and high-risk groups. The results demonstrate that the gene risk signature related to clinical features can be used as an independent prognostic indicator in glioma patients. Moreover, the high-risk subtype had rich immune infiltration and high expression of immune checkpoint genes in the tumor immune microenvironment (TIME). The analysis of the Submap algorithm shows that patients in the high-risk group could benefit more from anti-PD1 treatment. The risk characteristics associated with pyroptosis proposed in this study play an essential role in TIME and can potentially predict the prognosis and immunotherapeutic response of glioma patients.
神经胶质瘤是最常见的原发性脑肿瘤，高度恶性，预后不良。细胞焦亡是一种炎症形式的程序性细胞死亡，促进了癌症的炎症细胞死亡。研究表明，细胞焦亡可以促进癌症的炎症细胞死亡（ICD），从而影响癌症患者的预后。因此，控制细胞焦亡的基因可能是肿瘤治疗中有前途的候选生物标志物。本研究基于中国脑胶质瘤基因组图谱（CGGA）、癌症基因组图谱（TCGA）和分子脑肿瘤数据库（Rembrandt）数据库，研究了神经胶质瘤中与细胞焦亡相关的基因（PRGs）的功能。在本研究中，使用非负矩阵分解（NMF）聚类方法，从 RNA 测序数据中筛选出 26 个 PRGs，分为两个亚群。使用 LASSO 和 Cox 回归构建了一个由 4 个基因（BAX、Caspase-4、Caspase-8、PLCGl）组成的风险特征，并将 CGGA、TCGA 和 Rembrandt 队列中的所有神经胶质瘤患者分为低风险组和高风险组。结果表明，与临床特征相关的基因风险特征可作为神经胶质瘤患者的独立预后指标。此外，高风险亚型在肿瘤免疫微环境（TIME）中具有丰富的免疫浸润和高表达的免疫检查点基因。Submap 算法分析表明，高风险组患者可能从抗 PD1 治疗中获益更多。本研究提出的与细胞焦亡相关的风险特征在 TIME 中起着重要作用，可能有助于预测神经胶质瘤患者的预后和免疫治疗反应。
