Ren Jing, Xu Yixin, Liu Jia, Wu Sicheng, Zhang Ruihan, Cao Haowei, Sun Jinmin
Jiangsu Key Laboratory of Brain Disease Bioinformation, Research Center for Biochemistry and Molecular Biology, Xuzhou Medical University, Xuzhou, China.
Department of General Surgery, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Front Mol Biosci. 2021 Dec 23;8:779290. doi: 10.3389/fmolb.2021.779290. eCollection 2021.
MAP3K8 is a serine/threonine kinase that is widely expressed in immune cells, non-immune cells, and many tumor types. The expression, clinical significance, biological role, and the underlying molecular mechanisms of MAP3K8 in glioma have not been investigated yet. Here, we discovered that MAP3K8 was aberrantly overexpressed in glioma and correlated with poor clinicopathological features of glioma by analysis on different datasets and immunohistochemistry staining. MAP3K8 is an independent prognostic indicator and significantly correlates with the progression of glioma. We also performed the function and pathway enrichment analysis of MAP3K8 in glioma to explore its biological functions and underlying molecular mechanisms in glioma. MAP3K8 co-expressed genes were mainly enriched in immune-related biological processes such as neutrophil activation, leukocyte migration, neutrophil-mediated immunity, lymphocyte-mediated immunity, T-cell activation, leukocyte cell-cell adhesion, regulation of leukocyte cell-cell adhesion, B-cell-mediated immunity, myeloid cell differentiation, and regulation of cell-cell adhesion. Single-cell RNA sequencing data and immunohistochemistry analysis demonstrated that MAP3K8 is expressed in malignant and immune cells and mainly enriched in the microglia/macrophage cells of glioma. The expression of MAP3K8 was positively correlated with immune infiltration, including effector memory CD4 T cells, plasmacytoid dendritic cells, neutrophils, myeloid dendritic cells, mast cells, and macrophage in glioma. Further correlation analysis demonstrated that a series of inhibitory immune checkpoint molecules, chemokines, and chemokine receptors was positively correlated with the expression of MAP3K8. MAP3K8 might play an essential role in tumor immunity, and inhibition of MPA3K8 is a plausible strategy for glioma immunotherapy.
MAP3K8是一种丝氨酸/苏氨酸激酶，在免疫细胞、非免疫细胞和多种肿瘤类型中广泛表达。MAP3K8在胶质瘤中的表达、临床意义、生物学作用及潜在分子机制尚未见研究报道。在此，我们通过对不同数据集的分析和免疫组化染色发现，MAP3K8在胶质瘤中异常高表达，且与胶质瘤不良临床病理特征相关。MAP3K8是一个独立的预后指标，与胶质瘤进展显著相关。我们还对胶质瘤中MAP3K8进行了功能和通路富集分析，以探索其在胶质瘤中的生物学功能和潜在分子机制。MAP3K8共表达基因主要富集于免疫相关生物学过程，如中性粒细胞活化、白细胞迁移、中性粒细胞介导的免疫、淋巴细胞介导的免疫、T细胞活化、白细胞细胞间黏附、白细胞细胞间黏附调节、B细胞介导的免疫、髓样细胞分化以及细胞间黏附调节。单细胞RNA测序数据和免疫组化分析表明，MAP3K8在恶性细胞和免疫细胞中表达，主要富集于胶质瘤的小胶质细胞/巨噬细胞。MAP3K8的表达与免疫浸润呈正相关，包括效应记忆CD4 T细胞、浆细胞样树突状细胞、中性粒细胞、髓样树突状细胞、肥大细胞和胶质瘤中的巨噬细胞。进一步的相关性分析表明，一系列抑制性免疫检查点分子、趋化因子和趋化因子受体与MAP3K8的表达呈正相关。MAP3K8可能在肿瘤免疫中起重要作用，抑制MPA3K8是胶质瘤免疫治疗的一种可行策略。
