Lin Xuelei, Liu Hongwei, Zhao Hongyu, Xia Shunjin, Li Yueshuo, Wang Chaoqian, Huang Qi, Wanggou Siyi, Li Xuejun
Department of Neurosurgery, Xiangya Hospital, Central South University, Changsha, China.
Hunan International Scientific and Technological Cooperation Base of BrainTumor Research, Xiangya Hospital, Central South University, Changsha, China.
Front Oncol. 2022 Feb 2;12:842973. doi: 10.3389/fonc.2022.842973. eCollection 2022.
Mannosidase Alpha Class 2B Member 1 (MAN2B1) gene encodes lysosomal alpha-d-mannosidase involved in the ordered degradation of N-linked glycoproteins. Alteration in MAN2B1 has been proved to be accountable for several diseases. However, the relationship between MAN2B1 and glioma malignancy remains unclear. In this study, RNA-seq data from The Cancer Genome Atlas and the Chinese Glioma Genome Atlas datasets were analyzed to explore the correlation between MAN2B1 and clinicopathological features, prognosis, and somatic mutations in gliomas. We found that MAN2B1 was elevated in glioma and was correlated with malignant clinical and molecular features. Upregulated expression of MAN2B1 is prognostic for poor outcomes in glioma patients. Different frequencies of somatic mutations were found in gliomas between high and low MAN2B1 expression. Real-time quantitative polymerase chain reaction, western blot, and immunohistochemistry staining from glioma patient samples and cell lines were used to validate bioinformatic findings. Functional enrichment analysis showed that MAN2B1 was involved in immune and inflammation processes. Moreover, MAN2B1 expression was strongly correlated with M2 macrophages and weakly correlated with M1 macrophages. Further analysis confirmed that MAN2B1 was closely associated with the markers of M2 macrophages and tumor-associated macrophages. Taken together, MAN2B1 is a potential prognostic biomarker in glioma and associates with immune infiltration.
甘露糖苷酶α 2B类成员1（MAN2B1）基因编码参与N-连接糖蛋白有序降解的溶酶体α-D-甘露糖苷酶。已证明MAN2B1的改变是多种疾病的病因。然而，MAN2B1与胶质瘤恶性程度之间的关系仍不清楚。在本研究中，分析了来自癌症基因组图谱和中国胶质瘤基因组图谱数据集的RNA测序数据，以探讨MAN2B1与胶质瘤临床病理特征、预后和体细胞突变之间的相关性。我们发现MAN2B1在胶质瘤中升高，并且与恶性临床和分子特征相关。MAN2B1表达上调预示着胶质瘤患者预后不良。在MAN2B1高表达和低表达的胶质瘤中发现了不同频率的体细胞突变。使用来自胶质瘤患者样本和细胞系的实时定量聚合酶链反应、蛋白质印迹和免疫组织化学染色来验证生物信息学研究结果。功能富集分析表明，MAN2B1参与免疫和炎症过程。此外，MAN2B1表达与M2巨噬细胞强烈相关，与M1巨噬细胞弱相关。进一步分析证实，MAN2B1与M2巨噬细胞和肿瘤相关巨噬细胞的标志物密切相关。综上所述，MAN2B1是胶质瘤中一种潜在的预后生物标志物，并且与免疫浸润相关。
