【作者】 宋萍；

【导师】 张孟贤；

【作者基本信息】 华中科技大学 ， 肿瘤学（专业学位）， 2024， 硕士

【摘要】 目的:胶质瘤是中枢神经系统最常见的原发性恶性肿瘤。ALOX5AP是花生四烯酸转化为白三烯的关键酶,在多肿瘤中被认为与不良预后相关。然而,ALOX5AP与胶质瘤免疫微环境和预后的关系尚未完全阐明。方法:使用生物信息学分析胶质瘤中ALOX5AP的表达、ALOX5AP与免疫微环境的关系、ALOX5AP与胶质瘤治疗反应的关系、ALOX5AP的潜在功能以及ALOX5AP与预后的关系。通过多重免疫荧光染色验证ALOX5AP在胶质瘤中的表达和定位,并在胶质瘤组织芯片中验证ALOX5AP与预后的关系。结果:ALOX5AP在胶质瘤组织中高表达,与患者的WHO分级、年龄、性别、IDH突变状态、1p19q共缺失状态、MGMTp甲基化状态相关。单细胞测序结果显示ALOX5AP在巨噬细胞、小胶质细胞、单核细胞及T细胞中高表达,但在肿瘤细胞中几乎不表达。免疫浸润分析显示ALOX5AP的表达与M2巨噬细胞的浸润、多种免疫抑制因子、趋化因子及趋化因子受体相关。ALOX5AP高表达组的胶质瘤患者免疫应答率较低,对替莫唑胺的敏感性较差。富集分析显示,ALOX5AP与多种能量代谢过程、免疫细胞激活及免疫应答等通路相关。预后分析显示ALOX5AP与胶质瘤的不良预后有关,对胶质瘤患者的预后具有一定的预测作用。多重免疫荧光染色显示ALOX5AP表达于M2巨噬细胞中,同时验证了ALOX5AP与胶质瘤患者的不良预后相关。结论:ALOX5AP主要表达于胶质瘤的巨噬细胞中,且与M2巨噬细胞标记物共定位。ALOX5AP可作为预测胶质瘤免疫治疗反应和预后的潜在标记物,可能通过调节免疫微环境发挥促肿瘤作用,有望成为新的免疫治疗靶点。更多还原

【Abstract】 Objective: Glioma is the most common primary malignancies of the central nervous system.ALOX5 AP,a key enzyme in the conversion of arachidonic acid to leukotrienes,is thought to be associated with a poor prognosis in multiple tumors.However,the relationship between ALOX5 AP and the immune microenvironment and prognosis of gliomas has not been fully elucidated.Methods: Using bioinformatics analysis to investigate the expression of ALOX5 AP,its relationship to the immune microenvironment,its relationship to therapeutic response,its potential function,and its relationship to prognosis in gliomas.The expression and localization of ALOX5 AP in gliomas were verified by multiple immunofluorescence staining,and the relationship between ALOX5 AP and prognosis was verified in glioma tissue microarray.Results: ALOX5 AP was highly expressed in glioma tissues and correlated with WHO grade,age,gender,IDH mutation status,1p19 q co-deletion status,and MGMTp methylation status of glioma patients.Single-cell sequencing showed that ALOX5 AP was highly expressed in macrophages,microglia,monocytes,and T cells,but hardly expressed in tumor cells.Immune infiltration analysis showed that ALOX5 AP expression was associated with infiltration of M2 macrophages,multiple immunosuppressive factors,chemokines,and chemokine receptors.Glioma patients in the ALOX5 AP high-expression group had a low rate of immune response and were poorly sensitive to temozolomide.Enrichment analysis showed that ALOX5 AP was associated with pathways of energy metabolism,immune cell activation,and immune response.Prognostic analysis showed that ALOX5 AP was associated with poor prognosis of glioma,and was predictive of prognostic in glioma patients.Multiplex immunofluorescence staining showed that ALOX5 AP was expressed in M2 macrophages and also verified that ALOX5 AP was associated with poor prognosis of glioma patients.Conclusions: ALOX5 AP is predominantly expressed in macrophages of gliomas and colocalizes with the M2 macrophage marker.ALOX5 AP serves as a potential biomarker for predicting the response to and prognosis of immunotherapy in gliomas and may play a protumorigenic role by modulating the immune microenvironment,which is expected to be a new immunotherapeutic target.更多还原