基于生物信息学分析POFUT1表达与肿瘤免疫浸润水平及患者预后的相关性研究

Study on Correlation between Expression Level of POFUT1 and Tumor Immune Infiltration Level and Patient Prognosis Based on Bioinformatics Analysis

目的分析蛋白-O-岩藻糖基转移酶1(protein O-fucosyltransferase 1,POFUT1)表达与肿瘤免疫浸润水平及患者预后的关系,探索POFUT1在肿瘤免疫治疗方面的价值。方法基于泛癌数据利用R软件分析各类肿瘤组织中POFUT1表达水平变化及其与各类肿瘤患者风险比的相关性,筛选患者预后与POFUT1表达相关的肿瘤类型;利用String数据库构建蛋白质互作网络,筛选以POFUT1关联基因并进行功能富集分析;利用estimate包分析所筛选肿瘤组织POFUT1表达与免疫浸润评分的相关性;利用TIMER数据库分析肿瘤组织POFUT1表达与各类免疫细胞浸润水平的相关性及免疫细胞浸润水平与患者预后的相关性。结果POFUT1在14类肿瘤中的高水平表达差异具有统计学意义(均P<0.05),与低级别胶质瘤、肺腺癌、甲状腺癌的不良预后相关(Hazard Ratio>1,P<0.05);POFUT1及其关联基因高度参与Notch信号通路、淋巴细胞激活及免疫过程调控进程;POFUT1表达水平与低级别胶质瘤中的B细胞、CD8^(+)T细胞、CD4^(+)T细胞、巨噬细胞、中性粒细胞与树突状细胞、肺腺癌中的中性粒细胞、甲状腺癌中的B细胞、CD4^(+)T细胞及巨噬细胞的浸润程度均呈正相关(|r|>0.2,P<0.05);上述6类免疫细胞高浸润程度均与低级别胶质瘤患者较差的预后相关(Hazard Ratio>1,P<0.05)。结论POFUT1通过对免疫调控相关进程的高度参与,对部分肿瘤免疫浸润水平产生影响并影响患者预后,具有成为免疫治疗靶点的潜力。

Objective To analyze the relationship between expression level of protein O-fucosyltransferase 1(POFUT1)and tumor immune infiltration level and prognosis of patients,and explore the value of POFUT1 in tumor immunotherapy.Methods Based on the pan-cancer data,R software was used to analyze the changes in POFUT1 expression levels of various tumor tissues and their correlation with the risk ratio of various tumor patients,and screen for tumor types related to patient prognosis and POFUT1 expression.Through the String database,a protein interaction network was constructed,POFUT1-associated genes were screened,and functional enrichment analysis was performed.The estimate software package was used to analyze the correlation between POFUT1 expression and immune infiltration score in selected tumor tissues.The TIMER database was used to analyze the correlation between the expression level of POFUT1 and various levels of immune cell infiltration,and the correlation between the infiltration level of immune cells and the prognosis of patients.Results The expression levels of POFUT1 were significantly high in 14 types of tumors(P<0.05),and were associated with poor prognosis of low-grade gliomas,lung adenocarcinoma,and thyroid cancer(Hazard Ratio>1,P<0.05).POFUT1 and its associated genes were highly involved in Notch signaling pathway,lymphocyte activation and immune regulation processes.The expression level of POFUT1 was positively correlated with the infiltration degree of B cells,CD8^(+)T cells,CD4^(+)T cells,macrophages,neutrophils and dendritic cells in lowgrade gliomas,as well as positively associated with the infiltration level of neutrophils in LUAD,and B cells,CD4^(+)T cells and macrophages in thyroid cancer(|r|>0.2,P<0.05).The high infiltration levels of the above 6 types of immune cells were correlated with the poor prognosis of patients with low-grade glioma(Hazard Ratio>1,P<0.05).Conclusion POFUT1 was highly involved in the process of immune regulation,affecting the immune infiltration level of some tumors and further influencing patient prognosis.It may have the potential to become a target for tumor immunotherapy.