酸性核磷蛋白32A作为癌症中潜在的预后和免疫治疗生物标志物的泛癌分析研究  

An analysis of pan-cancer studies on the potential prognostic and immunotherapy biomarker of acidic nuclear phosphoprotein 32A in cancer

作　　者：王培培 吴亮亮 蔡磊 张宝玉 白怡冰 李金凤 Wang Peipei;Wu Liangliang;Cai Lei;Zhang Baoyu;Bai Yibing;Li Jinfeng(Zibo 148th Hospital,Zibo,Shandong255300,China;Institute of Tumor Medicine,Department of Tumor Medicine,Fifth Medical Center,PLA General Hospital,Beijing 100071,China)

机构地区：[1]淄博一四八医院,山东淄博255300 [2]解放军总医院第五医学中心,肿瘤医学部肿瘤研究所,北京100071

出　　处：《感染、炎症、修复》2024年第3期177-191,共15页Infection Inflammation Repair

摘　　要：目的:评估酸性核磷蛋白32A(ANP32A)与多种类型人类癌症的生存预后和免疫学调控的相关性。方法:ANP32A的差异表达分析基于基因型组织表达(GTEx)、癌症细胞系百科全书(CCLE)和癌症基因组图谱计划(TCGA)数据库的数据。采用COX回归检验和Kaplan-Meier检验进行预后分析,Spearman检验进行相关分析。利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)来富集相关信号通路。免疫组化(IHC)染色和蛋白免疫印记(western blot,WB)检测ANP32A和RNA结合蛋白人抗原R(HuR)在非小细胞肺癌中的表达,并分析两者之间的相关性。结果:在多种癌症中,肿瘤组织中的ANP32A表达明显高于正常组织,COX回归分析显示约10种癌症的ANP32A表达与预后有显著相关性,其中7种癌症类型中ANP32A高表达与不良总生存期相关,包括急性髓性白血病、肾上腺皮质癌和急性淋巴细胞白血病缓解期等。然而,在多形性低级别胶质瘤、肾透明细胞癌和胸腺瘤这3种癌症中,ANP32A高表达时患者预后良好。进一步分析表明,ANP32A表达与多种免疫检查点和免疫相关基因显著相关。此外,ANP32A与肿瘤微环境中免疫细胞浸润、RNA修饰、基因组异质性和肿瘤干性也存在密切关系。GO和KEGG分析显示,ANP32A参与调控信使RNA剪接加工、核糖核蛋白复合体生物发生和组蛋白修饰等信号通路。IHC数据表明在非小细胞肺癌中ANP32A和HuR的表达呈正相关,WB结果证实ANP32A能够诱导人非小细胞肺癌A549细胞系中HuR的表达,提示ANP32A可能通过调控HuR参与信使RNA剪接加工等生理过程。结论:ANP32A是一种新型肿瘤预后预测因子,并在肿瘤免疫细胞浸润、RNA修饰、基因组异质性、肿瘤干性和信使RNA剪接加工等方面发挥重要免疫学调控作用。Objective:To evaluate the association of acidic nuclear phosphoprotein 32A(ANP32A)with survival prognosis and immunological regulation of various types of human cancer.Methods:The differential expression analysis of ANP32A was based on genotype-tissue expression(GTEx),cancer cell line encyclopedia(CCLE)and the cancer genome atlas(TCGA)database.COX regression test and Kaplan-Meier test were used to analyze the prognosis.Spearman test was used for correlation analysis.The gene ontology(GO)and the Kyoto encyclopedia of genes and genomes(KEGG)were used to enrich the relevant signaling pathways.Immunohistochemistry(IHC)staining and western blot(WB)expression of ANP32A and RNA-binding protein human antigen R(HuR)in non-small cell lung carcinoma(NSCLC)were assessed,and the correlations between the two were also analyzed.Results:In most cancers,the expression of ANP32A in tumor tissues was significantly higher than that in normal tissues.COX regression analysis showed that the expression of ANP32A in about 10 cancers was significantly correlated with prognosis,and high expression of ANP32A in 7 cancer types was associated with adverse overall survival,including acute myeloid leukemia,adrenocortical carcinoma and acute lymphoblastic leukemia in remission stage,et al.However,in three cancers,such as glioblastoma multiforme low-grade glioma,kidney renal clear cell carcinoma,and thymoma,patients with high expression of ANP32A had a good prognosis.Further analysis showed that the expression of ANP32A was significantly correlated with multiple immune checkpoints and immune-related genes.In addition,ANP32A was also closely related to immune cell infiltration,RNA modification,genomic heterogeneity and tumor stemness in the tumor microenvironment.GO and KEGG analysis showed that ANP32A was involved in the regulation of messenger RNA splicing,ribonucleoprotein complex biogenesis and histone modification.IHC data showed a positive correlation between the expression of ANP32A and HuR in NSCLC.WB results confirmed that ANP32A could i

关 键 词：酸性核磷蛋白32A 泛癌 预后 免疫相关基因 RNA表观修饰 人抗原R 肿瘤 

分 类 号：R730.231[医药卫生—肿瘤]