基于生物信息学分析Midkine在胆管癌中的表达及其对预后的预测价值  

Expression of Midkine in cholangiocarcinoma and its value in predicting prognosis based on bioinformatics analysis

作　　者：谷月月 于书敏 常秀娟 高旭东 黄加干 贾晓东 曾珍 GU Yueyue;YU Shumin;CHANG Xiujuan;GAO Xudong;HUANG Jiagan;JIA Xiaodong;ZENG Zhen(The PLA 307 Clinical College of Anhui Medical University,The Fifth Clinical Medical College of Anhui Medical University,Hefei 230032,China;Senior Department of Hepatology,The Fifth Medical Center of Chinese PLA General Hospital,Beijing 100039,China;Peking University 302 Clinical Medical School,Beijing 100039,China;Senior Department of Oncology,The Fifth Medical Center of Chinese PLA General Hospital,Beijing 100071,China)

机构地区：[1]安徽医科大学解放军307临床学院,安徽医科大学第五临床医学院,合肥230032 [2]中国人民解放军总医院第五医学中心肝病医学部,北京100039 [3]北京大学三〇二临床医学院,北京100039 [4]中国人民解放军总医院第五医学中心肿瘤医学部,北京100071

出　　处：《临床肝胆病杂志》2024年第7期1428-1437,共10页Journal of Clinical Hepatology

基　　金：国家“十三五”科技重大专项课题(2018ZX10725-506-002);国家卫生健康委医药卫生科技发展研究中心(WKZX2023CX020011);北京市自然科学基金(7222172)。

摘　　要：目的研究中期因子(MDK)在胆管癌(CCA)中的表达及其对患者预后的预测价值,探索MDK可能影响CCA进展的机制。方法从癌症基因组图谱(TCGA)数据库获取CCA样本数据信息,分析MDK在癌与癌旁组织中的表达差异及其与临床特征的相关性,使用基因表达综合数据库(GEO)和解放军总医院第五医学中心2018年6月—2021年9月经手术切除的11例CCA患者的临床资料进行相关验证。通过STRING和Cytoscape构建蛋白互作网络,使用基因本体(GO)和京都基因与基因组数据库(KEGG)进行富集分析,探讨MDK相关基因所参与的生物学过程和肿瘤相关通路。此外,应用TIMER和TISIDB数据库分析CCA肿瘤组织中MDK的表达与免疫细胞浸润的相关性。计量资料两组间比较采用成组t检验或MannWhitney U检验。计数资料组间比较采用Fisher精确概率法。应用Kaplan-Meier法绘制生存曲线,并采用Log-rank检验进行组间比较。两变量间的相关性采用Spearman相关性分析。结果比较TCGA数据库中CCA患者肿瘤组织及癌旁组织中MDK的表达水平,非配对分析结果和配对分析结果均显示,MDK在CCA肿瘤组织中的表达水平高于癌旁组织(P值均<0.001);对纳入的11例CCA患者肿瘤组织及其配对癌旁组织标本进行转录组测序,结果显示,MDK在CCA肿瘤组织中的表达水平显著高于其配对癌旁组织(P<0.01)。MDK高表达与淋巴结转移(P=0.045)和血管侵犯(P=0.044)有关。生存分析显示,MDK高表达的CCA患者总生存期(χ^(2)=5.30,P=0.028)及疾病特异性生存期(χ^(2)=6.25,P=0.019)均明显短于MDK低表达的患者。GO和KEGG富集分析显示,MDK表达相关的30个基因与泛素介导的蛋白质水解过程密切相关,并影响CCA患者预后;TIMER分析结果显示,MDK表达与B淋巴细胞(r=0.356,P=0.0356)和树突状细胞(r=0.409,P=0.0147)在肿瘤组织微环境中的浸润呈正相关;TISIDB分析结果显示,MDK表达水平与CXCL16(r=0.465,P=0.00467)呈正相关,与CXCL12(Objective To investigate the expression of Midkine(MDK)in cholangiocarcinoma(CCA)and its value in predicting the prognosis of CCA,as well as the potential mechanism of the effect of MDK on the progression of CCA.Methods The data of CCA samples were obtained from TCGA database to analyze the difference in the expression of MDK between cancer tissue and paracancerous tissue and its association with clinical features,and the data collected from GEO database and 11 CCA patients who underwent surgical resection in The Fifth Medical Center of Chinese PLA General Hospital from June 2018 to September 2021 were used for validation.STRING and Cytoscape were used to construct a protein-protein interaction network,and gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analyses were used to investigate the biological functions and tumor-related pathways involving MDK-related genes.In addition,TIMER and TISIDB databases were used to analyze the correlation between MDK expression and immune cell infiltration in CCA tissue.The independent-samples t test or the Mann-Whitney U test was used for comparison of continuous data between two groups,and the Fisher’s exact test was used for comparison of categorical data between two groups.The Kaplan-Meier method was used to plot survival curves,and the Log-rank test was used for comparison between groups.The Spearman correlation analysis was used to investigate the correlation between two variables.Results The expression level of MDK in cancer tissue and paracancerous tissue of CCA patients was compared based on TCGA database,and the results of the non-paired and paired analyses showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in paracancerous tissue(P<0.001).Transcriptome sequencing was performed for the tumor tissue and its corresponding paracancerous tissue from 11 CCA patients,and the results showed that the expression level of MDK in CCA tumor tissue was significantly higher than that in corresponding paracanc

关 键 词：胆管上皮癌 中期因子 预后 

分 类 号：R735.8[医药卫生—肿瘤] Q811.4[医药卫生—临床医学]