利用数据库信息分析NAMPT与肝癌的病理特征和免疫浸润的关联性  

Association of NAMPT with pathological features and immune infiltration of hepatocellular carcinoma using database information

作　　者：常晴 刘佳[1,2] 曲爱林 杨咏梅[1,2] CHANG Qing;LIU Jia;QU Ailin;YANG Yongmei(Department of Clinical Laboratory,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China;Center for Basic Medical Research,Qilu Hospital of Shandong University,Jinan 250012,Shandong,China)

机构地区：[1]山东大学齐鲁医院检验医学中心,山东济南250012 [2]山东大学齐鲁医院基础医学研究中心,山东济南250012

出　　处：《山东大学学报（医学版）》2023年第4期26-36,共11页Journal of Shandong University:Health Sciences

基　　金：国家自然科学基金(82102481);山东省自然科学基金(ZR2021QH206)。

摘　　要：目的分析烟酰胺磷酸核糖转移酶(NAMPT)在肝细胞癌(HCC)中的表达,并研究其与肝癌患者病理特征及免疫浸润的关系。方法利用TIMER数据库获得NAMPT在HCC中的表达数据。通过UALCAN数据库分析NAMPT表达与血清甲胎蛋白(AFP)之间的相关性。从TCGA-LIHC中下载肝癌转录组RNA-Seq数据,提取NAMPT和免疫相关分子mRNA表达量。利用估计算法和单样本基因集富集分析(ssGSEA),评估NAMPT高低表达组间免疫成分、基质成分的数量和免疫细胞浸润丰度及计算免疫相关分子表达有无差异;分析NAMPT表达与免疫细胞浸润的关联性。结果TIMER数据库显示,NAMPT mRNA在HCC中的表达低于癌旁组织(P<0.05)。UALCAN数据库检测发现,NAMPT表达和血清AFP呈负向低度相关(r=-0.464,P<0.05)。基质细胞占比、免疫细胞占比和肿瘤细胞纯度在NAMPT高低表达组间存在统计学差异(P<0.05)。ssGSEA分析发现,20种免疫细胞在NAMPT高表达组中的浸润程度高于NAMPT低表达组(P<0.05)。免疫相关分子NKG2D、CD40、FAS、ELANE、PDL1、PDL2在两组中的表达差异有统计学意义(P<0.05)。TIMER数据库分析发现,NAMPT的表达与巨噬细胞(r=0.125,P=0.021)、中性粒细胞(r=0.284,P<0.001)和树突状细胞(r=0.131,P=0.016)浸润呈正向低度相关,与肿瘤纯度呈负向低度相关(r=-0.137,P=0.011)。结论NAMPT与临床病理参数具有一定相关性,并能在一定程度反映肝癌患者免疫微环境的状态。本研究为鉴别肝癌免疫治疗获益人群提供了新的线索。Objective To analyze the expression profile of nicotinamide phosphoribosyltransferase(NAMPT)in hepatocellular carcinoma(HCC),and to explore the relationship between NAMPT expression and immune infiltration and clinicopathological features.Methods The expression profile of NAMPT in HCC was obtained from TIMER database.Based on UALCAN database,the correlation between NAMPT and alpha fetal protein(AFP)level was analyzed.Hepatocellular carcinoma transcriptome RNA-seq dataset was downloaded from TCGA-LIHC,and the mRNA expressions of NAMPT and immune-related molecules were extracted.The number of immune components,matrix components and the abundance of immune cell infiltration and the differences in the expression of immune-related molecules between high-NAMPT and low-NAMPT groups were evaluated using the estimation algorithm and the single sample gene set enrichment analysis(ssGSEA),respectively.Differences of above variables were compared.The relevance between NAMPT and immune cell infiltration was analyzed.Results TIMER database showed that the expression of NAMPT in HCC was lower than that in adjacent tissues(P<0.05).UALCAN database revealed that there was a negative low correlation between NAMPT expression and serum AFP level(r=-0.464,P<0.05).There were significant differences in stromal cell proportion,immune cell proportion and tumor cell purity(P<0.05)between high-NAMPT and low-NAMPT groups.ssGSEA analysis identified the infiltration levels of 20 immune cells were higher in the high-NAMPT group(P<0.05).The expressions of immune-related genes including NKG2D,CD40,FAS,ELANE,PDL1 and PDL2 were significantly different between the two groups(P<0.05).TIMER database showed NAMPT had a low positive correlation with macrophages(r=0.125,P=0.021),neutrophils(r=0.284,P<0.001),and dendritic cells(r=0.131,P=0.016),but a low negative correlation with tumor purity(r=-0.137,P=0.011).Conclusion NAMPT expression is correlated with clinicopathological features,and can reflect the status of immune microenvironment in HCC patients.O

关 键 词：烟酰胺磷酸核糖转移酶 肝细胞癌 生物信息学 免疫浸润 肿瘤免疫微环境 

分 类 号：R574[医药卫生—消化系统]