四关节盒1基因在结直肠癌中的表达及其临床意义  

Expression of four-jointed box kinase 1 gene in colorectal cancer and its clinical significance

作　　者：樊佳鑫 梁超伟 梁超杰[2] 郭建昇[3] Fan Jiaxin;Liang Chaowei;Liang Chaojie;Guo Jiansheng(First Clinical Medical College,Shanxi Medical University,Taiyuan 030001,China;Department of Hepatobiliary and Pancreatic Surgery,First Hospital of Shanxi Medical University,Taiyuan 030001,China;Department of Gastrointestinal Surgery,First Hospital of Shanxi Medical University,Taiyuan 030001,China)

机构地区：[1]山西医科大学第一临床医学院,太原030001 [2]山西医科大学第一医院肝胆胰外科,太原030001 [3]山西医科大学第一医院胃肠外科,太原030001

出　　处：《肿瘤研究与临床》2022年第4期241-247,共7页Cancer Research and Clinic

基　　金：山西省青年科技研究基金(201901D211480)。

摘　　要：目的探讨四关节盒1(FJX1)基因在结直肠癌中的差异表达及其与预后的关系,以及相关作用机制。方法于2021年7月16日,从癌症基因组图谱(TCGA)数据库下载结直肠癌的转录组数据以及临床资料,分析FJX1 mRNA在结直肠癌肿瘤组织和癌旁组织中的表达情况、FJX1 mRNA与患者临床病理特征和预后的关系;绘制受试者工作特征(ROC)曲线,评估FJX1 mRNA预测结直肠癌患者生存的价值;采用Cox比例风险模型评估FJX1 mRNA是否为结直肠癌独立的预后影响因素。从基因表达综合(GEO)数据库中下载结直肠癌患者总生存(OS)时间和生存状态,分析FJX1 mRNA与预后的关系。从加州大学圣克鲁斯分校(UCSC xena)数据库中下载结直肠癌的甲基化数据,确定FJX1 mRNA各位点的甲基化程度及FJX1 mRNA的表达水平与各位点甲基化程度的相关性。采用基因集合富集分析法(GSEA)(4.1.0)分析结直肠癌中与FJX1 mRNA相关的信号通路。利用肿瘤免疫评估资源(TIMER)数据库研究FJX1 mRNA与肿瘤浸润免疫细胞的相关性。采用Spearman分析与小分子/药物敏感性分析探讨FJX1 mRNA表达水平与药物敏感性的相关性。结果TCGA数据库612例结直肠癌的转录组数据中,FJX1 mRNA在肿瘤组织中较癌旁组织高表达(P<0.001);549例有完整资料结直肠癌患者FJX1 mRNA表达与M分期(P=0.007)、病理分期(Ⅳ期比Ⅰ期,P=0.016;Ⅳ期比Ⅱ期,P=0.03;Ⅳ期比Ⅲ期,P=0.012)相关,与年龄、性别、T分期、N分期均无关(均P>0.05)。TCGA数据库和GEO数据库中,按照FJX1 mRNA表达量的中位值将患者分为高表达组和低表达组,FJX1 mRNA高表达组OS均较低表达组差(均P<0.05)。利用TCGA数据库中数据绘制FJX1 mRNA表达对结直肠癌患者1、3、5年OS率的ROC曲线,曲线下面积(AUC)分别为0.595、0.625、0.764。多因素Cox回归分析结果显示年龄(HR=1.050,95%CI 1.028~1.073,P<0.001)、T分期(HR=1.787,95%CI 1.090~2.927,P=0.021)和FJX1 mRNA高表达(HR=1.160,95%CObjective To investigate the differential expression of four-jointed box kinase 1(FJX1)gene in colorectal cancer and its relationship with prognosis and the related mechanisms.Methods On July 16,2021,the transcriptome data and clinical data of colorectal cancer were downloaded from The Cancer Genome Atlas(TCGA)database to analyze the expressions of FJX1 mRNA in colorectal cancer tissues and paracancerous tissues,and the relationship between FJX1 mRNA and clinicopathological characteristics and prognosis of patients.Receiver operating characteristic(ROC)curve was drawn to evaluate the value of FJX1 mRNA in predicting the survival of patients with colorectal cancer.Cox proportional hazards model was used to evaluate whether FJX1 mRNA was an independent influencing factor for prognosis of colorectal cancer.The overall survival(OS)time and survival status of colorectal cancer patients were downloaded from the Gene Expression Omnibus(GEO)database,and the relationship between FJX1 mRNA and prognosis of patients was analyzed.The methylation data of colorectal cancer was downloaded from the University of California,Santa Cruz(UCSC xena)database to determine the degree of methylation at each site of FJX1 mRNA and the correlation between the expression of FJX1 mRNA and the degree of methylation at each site.Signaling pathways associated with FJX1 mRNA in colorectal cancer were analyzed by using the Gene Set Enrichment Analysis(GSEA)(4.1.0).The correlation between FJX1 mRNA and tumor-infiltrating immune cells was investigated by using the Tumor Immunity Evaluation Resource(TIMER)database.Spearman analysis and small molecule/drug sensitivity analysis were used to explore the correlation between FJX1 mRNA expression and drug sensitivity.Results In the transcriptome data of 612 colorectal cancer cases in TCGA database,the expression of FJX1 mRNA in colorectal cancer tissues was higher than that in the paracancerous tissues(P<0.001).In 549 colorectal cancer patients with complete data,FJX1 mRNA expression was correlated with M

关 键 词：结直肠肿瘤 计算生物学 肿瘤微环境 预后 四关节盒1 

分 类 号：R735.34[医药卫生—肿瘤]