Department of Oncology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Hubei, Wuhan, 430030, P.R. China.
BMC Med Genomics. 2024 Aug 21;17(1):218. doi: 10.1186/s12920-024-01991-8.
Treatment of gliomas, the most prevalent primary malignant neoplasm of the central nervous system, is challenging. Arachidonate 5-lipoxygenase activating protein (ALOX5AP) is crucial for converting arachidonic acid into leukotrienes and is associated with poor prognosis in multiple cancers. Nevertheless, its relationship with the prognosis and the immune microenvironment of gliomas remains incompletely understood.
The differential expression of ALOX5AP was evaluated based on public Databases. Kaplan-Meier, multivariate Cox proportional hazards regression analysis, time-dependent receiver operating characteristic, and nomogram were used to estimate the prognostic value of ALOX5AP. The relationship between ALOX5AP and immune infiltration was calculated using ESTIMATE and CIBERSORT algorithms. Relationships between ALOX5AP and human leukocyte antigen molecules, immune checkpoints, tumor mutation burden, TIDE score, and immunophenoscore were calculated to evaluate glioma immunotherapy response. Single gene GSEA and co-expression network-based GO and KEGG enrichment analysis were performed to explore the potential function of ALOX5AP. ALOX5AP expression was verified using multiplex immunofluorescence staining and its prognostic effects were confirmed using a glioma tissue microarray.
ALOX5AP was highly expressed in gliomas, and the expression level was related to World Health Organization (WHO) grade, age, sex, IDH mutation status, 1p19q co-deletion status, MGMTp methylation status, and poor prognosis. Single-cell RNA sequencing showed that ALOX5AP was expressed in macrophages, monocytes, and T cells but not in tumor cells. ALOX5AP expression positively correlated with M2 macrophage infiltration and poor immunotherapy response. Immunofluorescence staining demonstrated that ALOX5AP was upregulated in WHO higher-grade gliomas, localizing to M2 macrophages. Glioma tissue microarray confirmed the adverse effect of ALOX5AP in the prognosis of glioma.
ALOX5AP is highly expressed in M2 macrophages and may act as a potential biomarker for predicting prognosis and immunotherapy response in patients with glioma.
治疗脑胶质瘤，即中枢神经系统最常见的原发性恶性肿瘤，极具挑战性。花生四烯酸 5-脂氧合酶激活蛋白（ALOX5AP）在将花生四烯酸转化为白三烯的过程中至关重要，并且与多种癌症的不良预后相关。然而，其与脑胶质瘤的预后和免疫微环境的关系仍不完全清楚。
基于公共数据库评估 ALOX5AP 的差异表达。采用 Kaplan-Meier 法、多变量 Cox 比例风险回归分析、时间依赖性接收者操作特征曲线和列线图评估 ALOX5AP 的预后价值。采用 ESTIMATE 和 CIBERSORT 算法计算 ALOX5AP 与免疫浸润的关系。计算 ALOX5AP 与人类白细胞抗原分子、免疫检查点、肿瘤突变负荷、TIDE 评分和免疫表型评分的关系，以评估脑胶质瘤免疫治疗反应。进行单基因 GSEA 以及基于共表达网络的 GO 和 KEGG 富集分析，以探索 ALOX5AP 的潜在功能。采用多重免疫荧光染色验证 ALOX5AP 的表达，并通过脑胶质瘤组织微阵列验证其预后作用。
ALOX5AP 在脑胶质瘤中高表达，其表达水平与世界卫生组织（WHO）分级、年龄、性别、IDH 突变状态、1p19q 共缺失状态、MGMTp 甲基化状态和不良预后相关。单细胞 RNA 测序显示 ALOX5AP 在巨噬细胞、单核细胞和 T 细胞中表达，但不在肿瘤细胞中表达。ALOX5AP 表达与 M2 巨噬细胞浸润和不良免疫治疗反应呈正相关。免疫荧光染色显示 ALOX5AP 在 WHO 分级较高的脑胶质瘤中上调，定位于 M2 巨噬细胞。脑胶质瘤组织微阵列证实 ALOX5AP 对脑胶质瘤的预后有不良影响。
ALOX5AP 在 M2 巨噬细胞中高表达，可能成为预测脑胶质瘤患者预后和免疫治疗反应的潜在生物标志物。
