摘要
目的分析ADAP2基因与肺鳞癌患者预后及其与肿瘤微环境免疫细胞浸润的关联。方法下载TCGA(The Cancer Genome Atlas)数据库肺鳞癌患者临床信息和癌组织ADAP2基因转录水平,运用KM生存曲线和Cox比例风险模型分析ADAP2基因和患者预后的关联;采用xCell数据库分析ADAP2基因表达和肿瘤微环境免疫浸润的关系;利用免疫荧光双染实验观察ADAP2蛋白与M2型巨噬细胞标志物CD163的空间共定位。结果多因素Cox分析结果显示,ADAP2表达是肺鳞癌患者独立的预后因素,其高表达与肺鳞癌患者不良预后密切相关(HR=1.533,95%CI:1.139~2.064,P=0.005)。ADAP2基因与肿瘤微环境评分呈正相关(r=0.609,95%CI:0.550~0.661,P<0.001),与免疫评分也同样呈正相关(r=0.596,95%CI:0.536~0.650,P<0.001)。ADAP2基因与肺鳞癌单核吞噬细胞系统(巨噬细胞、巨噬细胞M1、巨噬细胞M2、单核细胞)的浸润呈高度正相关(r=0.737、0.718、0.603、0.631,P<0.001)。ADAP2与CD163存在共定位,主要表达于细胞膜。结论ADAP2有望成为预测肺鳞癌患者预后和免疫治疗效果的潜在生物标志物。
Objective To investigate the correlation between ADAP2 gene and immune infiltration in tumor microenvironment in lung squamous cell carcinoma(LUSC), and to explore the prognostic values of ADAP2 in patients with LUSC. Methods The clinical information of patients with LUSC as well as the data of ADAP2 mRNA levels in cancer tissues were downloaded from The Cancer Genome Atlas(TCGA) database. The association between ADAP2 gene and prognosis of patients was subsequently analyzed using Kaplan-Meier survival curve and Cox risk model analyses. xCell database was adopted to analyze the correlation of ADAP2 expression with immune infiltration in tumor microenvironment. Immunofluorescence double-staining test was employed to observe the co-localization of ADAP2 protein and CD163(a specific biomarker of M2 macrophage). Results Multivariate Cox analysis showed that the expression of ADAP2 was an independent prognostic factor for LUSC patients, and its high expression was closely associated with the poor prognosis of patients(HR=1.533, 95%CI: 1.139~2.064, P=0.005). xCell analysis indicated that ADAP2 gene was positively correlated with both the tumor microenvironment score(r=0.609, 95%CI: 0.550~0.661, P<0.001), and the immune infiltration score(r=0.596, 95%CI: 0.536~0.650, P<0.001), and the expression of ADAP2 also showed a high positive association with mononuclear phagocyte system(macrophage, macrophage M1, macrophage M2 and monocyte) in LUSC(r=0.737, 0.718, 0.603 and 0.631, respectively, P<0.001). Moreover, ADAP2 presented co-localization with CD163 and was mainly expressed in the cell membrane. Conclusion ADAP2 can act as a potential biomarker for predicting prognosis and evaluating the efficacy of immunotherapy in LUSC.
作者
陈峥
向颖
邬娜
夏婷婷
单亦凡
谢薇佳
许斌
袁志权
胡琴
贾潇岳
吴龙
李亚斐
CHEN Zheng;XIANG Ying;WU Na;XIA Tingling;SHAN Yifan;XIE Weijia;XU Bin;YUAN Zhiquan;HU Qin;JIA Xiaoyue;WU Long;LI Yafei(Department of Military Epidemiology,Faculty of Military Preventive Medicine,Army Medical University(Third Military Medical University),Chongqing,400038,China)
出处
《陆军军医大学学报》
CAS
CSCD
北大核心
2022年第4期337-345,共9页
Journal of Army Medical University
基金
国家自然科学基金面上项目(81871896)。
关键词
肺鳞癌
ADAP2
肿瘤免疫微环境
预后
生物信息分析
xCell算法
lung squamous cell carcinoma
ADAP2
tumor immune microenvironment
prognosis
bioinformatics analysis
xCell algorithm
