Zeng Yingying, Tan Peixin, Ren Chen, Gao Lianxuan, Chen Yulei, Hu Shushu, Tang Nan, Chen Chen, Du Shasha
Department of Radiation Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, China.
Department of Radiology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.
Front Genet. 2022 Jun 6;13:795844. doi: 10.3389/fgene.2022.795844. eCollection 2022.
Glioma is the most common malignancy of the nervous system with high mortality rates. The MS4A family members have been reported as potential prognostic biomarkers in several cancers; however, the relationship between the MS4A family and glioma has not been clearly confirmed. In our study, we explored the prognostic value of MS4As as well as their potential pro-cancer mechanisms of glioma. Using bioinformatics analysis methods based on the data from public databases, we found that the expression of MS4A4A, MS4A4E, MS4A6A, MS4A7, TMEM176A, and TMEM176B was significantly overexpressed in glioma tissues compared with that of normal tissues. The Kaplan-Meier method and Cox proportional hazards models revealed that high levels of MS4As can be associated with a poorer prognosis; TMEM176A, TMEM176B, age, WHO grade, and IDH status were identified as independent prognostic factors. Enrichment analysis predicted that MS4As were related to tumor-related pathways and immune response, which might regulate the process of MS4As promoting tumorigenesis. Additionally, we analyzed the correlations of MS4A expression with immune cells and immune inhibitory molecules. Finally, data from the cell culture suggested that knockdown of the TMEM176B gene contributes to the decreased proliferation and migration of glioma cells. In conclusion, MS4A4A, MS4A4E, MS4A6A, MS4A7, TMEM176A, and TMEM176B may act as potential diagnostic or prognostic biomarkers in glioma and play a role in forming the immune microenvironment in gliomas.
神经胶质瘤是最常见的神经系统恶性肿瘤,死亡率很高。MS4A家族成员已被报道为几种癌症中的潜在预后生物标志物;然而,MS4A家族与神经胶质瘤之间的关系尚未得到明确证实。在我们的研究中,我们探讨了MS4A的预后价值及其在神经胶质瘤中的潜在促癌机制。基于公共数据库的数据,使用生物信息学分析方法,我们发现与正常组织相比,MS4A4A、MS4A4E、MS4A6A、MS4A7、TMEM176A和TMEM176B在神经胶质瘤组织中的表达显著上调。Kaplan-Meier方法和Cox比例风险模型显示,高水平的MS4A与较差的预后相关;TMEM176A、TMEM176B、年龄、世界卫生组织分级和异柠檬酸脱氢酶状态被确定为独立的预后因素。富集分析预测,MS4A与肿瘤相关途径和免疫反应有关,这可能调节MS4A促进肿瘤发生的过程。此外,我们分析了MS4A表达与免疫细胞和免疫抑制分子的相关性。最后,细胞培养数据表明,敲低TMEM176B基因有助于降低神经胶质瘤细胞的增殖和迁移。总之,MS4A4A、MS4A4E、MS4A6A、MS4A7、TMEM176A和TMEM176B可能作为神经胶质瘤潜在的诊断或预后生物标志物,并在神经胶质瘤免疫微环境的形成中发挥作用。