Wang Zhi-Liang, Huang Ruo-Yu, Han Bo, Wu Fan, Sun Zhi-Yan, Li Guan-Zhang, Zhang Wei, Zhao Zheng, Liu Xing
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, People's Republic of China.
Department of Molecular Neuropathology, Beijing Neurosurgical Institute, Capital Medical University, No. 119 South 4th Ring West Road, Beijing, 100070, People's Republic of China.
Chin Neurosurg J. 2022 Oct 28;8(1):34. doi: 10.1186/s41016-022-00301-4.
mRNA became a promising therapeutic approach in many diseases. This study aimed to identify the tumor antigens specifically expressed in tumor cells for lower-grade glioma (LGG) and glioblastoma (GBM) patients.
In this work, the mRNA microarray expression profile and clinical data were obtained from 301 samples in the Chinese Glioma Genome Atlas (CGGA) database, the mRNA sequencing data and clinical data of 701 samples were downloaded from The Cancer Genome Atlas (TCGA) database. Genetic alterations profiles were extracted from CGGA and cBioPortal datasets. R language and GraphPad Prism software were applied for the statistical analysis and graph work.
PTBP1 and SLC39A1, which were overexpressed and indicated poor prognosis in LGG patients, were selected as tumor-specific antigens for LGG patients. Meanwhile, MMP9 and SLC16A3, the negative prognostic factors overexpressed in GBM, were identified as tumor-specific antigens for GBM patients. Besides, three immune subtypes (LGG1-LGG3) and eight WGCNA modules were identified in LGG patients. Meanwhile, two immune subtypes (GBM1-GBM2) and 10 WGCNA modules were selected in GBM. The immune characteristics and potential functions between different subtypes were diversity. LGG2 and GBM1 immune subtype were associated with longer overall survival than other subtypes.
In this study, PTBP1 and SLC39A1 are promising antigens for mRNA vaccines development in LGG, and MMP9 and SLC16A3 were potential antigens in GBM. Our analyses indicated that mRNA vaccine immunotherapy was more suitable for LGG2 and GBM1 subtypes. This study was helpful for the development of glioma immunotherapies.
信使核糖核酸（mRNA）在多种疾病中成为一种有前景的治疗方法。本研究旨在鉴定低级别胶质瘤（LGG）和胶质母细胞瘤（GBM）患者肿瘤细胞中特异性表达的肿瘤抗原。
在本研究中，从中国胶质瘤基因组图谱（CGGA）数据库的301个样本中获取mRNA微阵列表达谱和临床数据，从癌症基因组图谱（TCGA）数据库下载701个样本的mRNA测序数据和临床数据。从CGGA和cBioPortal数据集中提取基因改变图谱。应用R语言和GraphPad Prism软件进行统计分析和绘图工作。
在LGG患者中过表达且提示预后不良的多聚嘧啶结合蛋白1（PTBP1）和溶质载体家族39成员1（SLC39A1）被选为LGG患者的肿瘤特异性抗原。同时，在GBM中过表达的负性预后因子基质金属蛋白酶9（MMP9）和溶质载体家族16成员3（SLC16A3）被鉴定为GBM患者的肿瘤特异性抗原。此外，在LGG患者中鉴定出三种免疫亚型（LGG1-LGG3）和八个加权基因共表达网络分析（WGCNA）模块。同时，在GBM中选择了两种免疫亚型（GBM1-GBM2）和10个WGCNA模块。不同亚型之间的免疫特征和潜在功能存在差异。LGG2和GBM1免疫亚型的总生存期比其他亚型更长。
在本研究中，PTBP1和SLC39A1是LGG中mRNA疫苗开发的有前景的抗原，而MMP9和SLC16A3是GBM中的潜在抗原。我们的分析表明，mRNA疫苗免疫疗法更适合LGG2和GBM1亚型。本研究有助于胶质瘤免疫疗法的发展。
