Animal Molecular Biochemistry Laboratory, Department of Animal Science, College of Agriculture and Life Sciences, Chonnam National University, Gwangju, 61186, Republic of Korea.
Computational Biology and Bioinformatics Laboratory, Department of Integrative Biotechnology, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419, Republic of Korea.
Sci Rep. 2024 Sep 27;14(1):22159. doi: 10.1038/s41598-024-72901-2.
Glioblastoma multiforme (GBM) is the most aggressive type of primary brain tumor, and the presence of glioma stem cells (GSCs) has been linked to its resistance to treatments and recurrence. Additionally, aberrant glycosylation has been implicated in the aggressiveness of cancers. However, the influence and underlying mechanism of N-glycosylation on the GSC phenotype and GBM malignancy remain elusive. Here, we performed an in-silico analysis approach on publicly available datasets to examine the function of N-glycosylation-related genes in GSCs and gliomas, accompanied by a qRT-PCR validation experiment. We found that high α-1,2-mannosidase MAN1C1 is associated with immunological functions and worse survival of glioma patients. Differential gene expression analysis and qRT-PCR validation revealed that MAN1C1 is highly expressed in GSCs. Furthermore, higher MAN1C1 expression predicts worse outcomes in glioma patients. Also, MAN1C1 expression is increased in the perinecrotic region of GBM and is associated with immunological and inflammatory functions, a hallmark of the GBM mesenchymal subtype. Further analysis confirmed that MAN1C1 expression is closely associated with infiltrating immune cells and disrupted immune response in the GBM microenvironment. These suggest that MAN1C1 is a potential biomarker for gliomas and may be important as an immunotherapeutic target for GBM.
多形性胶质母细胞瘤（GBM）是最具侵袭性的原发性脑肿瘤，而神经胶质瘤干细胞（GSCs）的存在与它对治疗的耐药性和复发有关。此外，异常的糖基化与癌症的侵袭性有关。然而，N-糖基化对 GSC 表型和 GBM 恶性程度的影响及其潜在机制仍不清楚。在这里，我们通过公共数据集进行了计算机分析，以研究 N-糖基化相关基因在 GSCs 和神经胶质瘤中的功能，并进行了 qRT-PCR 验证实验。我们发现高表达的α-1,2-甘露糖苷酶 MAN1C1 与免疫功能和神经胶质瘤患者的生存不良有关。差异基因表达分析和 qRT-PCR 验证表明，MAN1C1 在 GSCs 中高表达。此外，MAN1C1 表达水平越高，预示着神经胶质瘤患者的预后越差。此外，MAN1C1 在 GBM 的坏死周围区域表达增加，与免疫和炎症功能有关，这是 GBM 间质亚型的一个标志。进一步的分析证实，MAN1C1 的表达与浸润免疫细胞密切相关，并破坏了 GBM 微环境中的免疫反应。这些表明，MAN1C1 是神经胶质瘤的一个潜在生物标志物，可能作为 GBM 的免疫治疗靶点很重要。
