食管癌组织ARL5B表达与临床病理特征的关系及作用机制  

Expression and clinicopathologic features of ARL5B in esophageal cancer and its mechanism

作　　者：赵小涵 盖春月 王鹤松 王多[3] 檀碧波[4] 沈文斌[1] ZHAO Xiaohan;GAI Chunyue;WANG Hesong;WANG Duo;TAN Bibo;SHEN Wenbin(The Third Radiotherapy Department of the Fourth Hospital Attached to Hebei Medical University,Shijiazhuang 050011;The Throacic Surgery Department of the Fourth Hospital Attached to Hebei Medical University,Shijiazhuang 050011;College of Life Sciences,Hebei Normal University,Shijiazhuang 050010;The Third General Surgery Department of the Fourth Hospital Attached to Hebei Medical University,Shijiazhuang 050011,China)

机构地区：[1]河北医科大学第四医院放三科,河北石家庄050011 [2]河北医科大学第四医院胸外科,河北石家庄050011 [3]河北师范大学生命科学学院,河北石家庄050010 [4]河北医科大学第四医院外三科,河北石家庄050011

出　　处：《西安交通大学学报（医学版）》2024年第2期237-243,共7页Journal of Xi’an Jiaotong University（Medical Sciences）

基　　金：河北省科技厅卫生健康创新专项资助项目(No.21377785D)。

摘　　要：目的应用生物信息学技术探讨ARL5B的临床意义及可能的潜在作用机制,并通过临床资料、基础实验等进行了初步验证。方法从TCGA数据库下载食管癌数据集,R软件分析差异表达的mRNA,结合患者的临床数据集进行生存分析。取临床食管癌及癌旁组织标本,采用实时定量PCR(qRT-PCR)及蛋白印迹(Western blotting)验证ARL5B表达。免疫组化检测ARL5B表达并评价其与食管癌患者临床病理特征的关系。利用生物信息学对ARL5B潜在作用机制初步分析,qRT-PCR初步验证可能与其作用的基因。结果生物信息学结果显示ARL5B在人食管癌组织中的表达明显高于癌旁组织且ARL5B高表达是食管癌患者预后差的标志。淋巴结组织、肿瘤组织、癌旁组织中,ARL5B的mRNA和蛋白的表达由高到低,与生物信息学结果符合。临床分析表明ARL5B表达与肿瘤的淋巴结转移、临床分期有关,其高表达是患者预后差的标志。富集分析显示ARL5B与囊泡传输、内体传输、细胞器定位等生物学过程有关。蛋白质-蛋白质相互作用(protein-protein interaction,PPI)分析提示与ARL5B互作的蛋白质有VPS16、KIF1A、TOM1等。qRT-PCR验证表明,VPS16、KIF1A、TOM1的mRNA在食管癌组织中表达高于癌旁组织(n=60)且与ARL5B表达呈正相关。结论食管癌中ARL5B存在高表达,与肿瘤淋巴结转移、临床分期及预后有关;ARL5B可能通过多种分子机制调控参与食管癌进展。Objective To evaluate the clinical implications of ARL5B in esophageal cancer and its underlying mechanisms by using bioinformatics methods.Methods ARL5B transcriptomic expression data were obtained from The Cancer Genome Atlas(TCGA),R software was employed to detect the differential expression mRNAs,and related clinical information was collected for survival analysis.To validate the bioinformatics results,Real-time quantitative PCR(qRT-PCR) and Western blotting were carried out for clinical specimens of esophageal cancer tumor tissues and adjacent tissues.Immunohistochemistry was used to evaluate the expression of ARL5B and its associated clinicopathologic features.The underlying mechanisms of ARL5B in esophageal cancer were preliminarily explored by bioinformatics and qRT-PCR.Results Bioinformatics method showed that the expression of ARL5B in human esophageal cancer tissues was significantly higher than in adjacent tissues and correlated with poor prognosis.Clinical specimens were detected,the expressions of ARL5B mRNA and protein were the highest in metastases lymph node,followed by esophageal cancer tissues and adjacent tissues,which corresponded with bioinformatics results.The expression of ARL5B was strongly correlated with lymph node metastases and advanced clinical stage.Kaplan-Meier analysis results denoted high ARL5B level,indicating poor prognosis.Enrichment analysis showed that ARL5B was associated the biological processes such as vacuolar transport,late endosome to lysosome transport,and organelle localization.Protein-protein interaction analysis(PPI) suggested that ARL5B might interact with VPS16,KIF1A and TOM1,whose expressions were verified by qRT-PCR and positively correlated with ARL5B expression.Conclusion ARL5B was highly expressed in esophageal cancer and associated with lymph node metastases,advanced clinical stage,and poor prognosis.ARL5B may be involved in the progression of esophageal cancer with several molecular mechanisms.

关 键 词：食管癌 ADP-核糖基化样因子5B(ARL5B) 临床病理学特征 KAPLAN-MEIER法 生物信息学分析 

分 类 号：R735.1[医药卫生—肿瘤]