HMMR基因与肺腺癌患者预后及浸润性免疫细胞关系的生物信息学分析  

Bioinformatics analysis of relationship between HMMR gene,prognosis and infiltrating immune cells in patients with lung adenocarcinoma

作　　者：余军林 李兰[2] 李向荣 YU Junlin;LI Lan;LI Xiangrong(Department of Oncology,Xiaogan Hospital Affiliated to Wuhan University of Science and Technology,Xiaogan 432000,China)

机构地区：[1]武汉科技大学附属孝感医院肿瘤科,孝感432000 [2]昆明医科大学附属第三医院肿瘤科,昆明650118

出　　处：《中国免疫学杂志》2023年第9期1943-1949,共7页Chinese Journal of Immunology

基　　金：孝感市自然科学计划项目(XGKJ2021010052)。

摘　　要：目的:透明质酸介导的运动受体(HMMR)基因在多种肿瘤中异常表达,然而,其在肺腺癌(LUAD)中的预后价值及与浸润性淋巴细胞的关系未知,因此,本文着重研究HMMR在LUAD中的预后价值及与浸润性免疫细胞的关系。方法:从TCGA数据库下载LUAD组织和正常组织间的转录表达谱及相应临床信息。通过RT-PCR反应评估LUAD细胞系及正常支气管上皮细胞系HMMR的表达水平。通过临床蛋白质组学肿瘤分析联盟(CPTAC)评估HMMR蛋白表达情况。受试者工作特征(ROC)曲线用于区分LUAD组织与邻近正常组织。通过单因素及多因素Cox分析及Kaplan-Meier方法评估HMMR对患者预后的影响。通过STRING构建蛋白质-蛋白质相互作用(PPI)网络。采用R语言“ClusterProfiler”包进行功能富集分析。通过TIMER评估HMMR在不同肿瘤中的表达情况及与LUAD浸润性免疫细胞浸润丰度间的关系。结果:HMMR在肺腺癌组织及细胞系中的表达较邻近正常组织或正常支气管上皮细胞系中显著上调。HMMR表达增加与吸烟超过40年、R1或R2残留肿瘤、高T分期、淋巴结转移、远处转移和高TNM分期相关。Kaplan-Meier生存分析显示,HMMR高表达组的LUAD患者预后较低表达组患者差(41.9个月vs 59.9个月,P<0.001),各亚组分析也显示相似的结果。ROC曲线分析表明,在截断水平为2.103的情况下,HMMR区分LUAD与相邻对照的敏感性和特异性分别为98.3%和86.2%。相关分析表明,HMMR的表达水平与肿瘤浸润性免疫细胞的浸润丰度相关。结论:HMMR表达上调与LUAD预后不良和免疫浸润显著相关,可以作为LUAD预后不良的生物标志物及免疫治疗靶点。Objective:Hyaluronic acid-mediated motor receptor(HMMR)gene is abnormally expressed in a variety of tumor types.However,its prognostic value in lung adenocarcinoma(LUAD)and its relationship with infiltrating lymphocytes are unknown Therefore,this study focuses on the prognostic value of HMMR in LUAD and the correlation of infiltrating immune cells.Methods:Transcriptional expression profile between lung adenocarcinoma tissue and normal tissue and the corresponding clinical information were downloaded from TCGA database.Expression level of HMMR in LUAD cell line and normal bronchial epithelial cell line were assessed by RT-PCR.HMMR protein expression was evaluated by Clinical Proteomics Tumor Analysis Consortium(CPTAC).Receiver operating characteristic(ROC)curve was used to distinguish LUAD tissue and adjacent normal tissues.Univariate and multivariate Cox analysis and Kaplan-Meier method were used to evaluate the impact of HMMR on prognosis of patients.A protein-protein interaction(PPI)network was constructed through STRING.R language"ClusterProfiler"package was used for functional enrichment analysis.TIMER was used to evaluate the expression of HMMR in different tumors and its relationship with the abundance of infiltrating immune cells in LUAD.Results:Expression of HMMR in LUAD tissues and cell line was significantly up-regulated compared with adjacent normal tissues and normal bronchial epithelial cell line.Increased HMMR expression was related to smoking for more than 40 years,R1 or R2 residual tumor,high T stage,lymph node metastasis,distant metastasis and high TNM stage.Kaplan-Meier survival analysis showed that the prognosis of LUAD patients in high HMMR expression group was worse than that in low HMMR expression group(41.9 months vs 59.9 months,P<0.001),and the analysis of each subgroup also showed similar results.ROC curve analysis showed that with a cut-off level of 2.103,sensitivity and specificity of HMMR to distinguish LUAD from adjacent controls were 98.3%and 86.2%,respectively.Correlation analysis s

关 键 词：HMMR 肺腺癌 生物标志物 预后 免疫浸润 

分 类 号：R392.1[医药卫生—免疫学]