TIMP1与EFEMP1在直肠癌中的表达水平及预后意义  

Expression level and prognostic significance of TIMP1 and EFEMP1 in rectal cancer

作　　者：谭莹 练国达[1] 陈少杰[1] 李佳佳[1] 陈尚祥 黄开红[1] 陈茵婷[1] TAN Ying;LIAN Guo-da;CHEN Shao-jie;LI Jia-jia;CHEN Shang-xiang;HUANG Kai-hong;CHEN Yin-ting(Department of Gastroenterology,Sun Yat-sen Memorial Hospital,Sun Yat-sen University,Guangzhou 510120,China)

机构地区：[1]中山大学孙逸仙纪念医院消化科,广州510120

出　　处：《岭南现代临床外科》2020年第2期161-166,共6页Lingnan Modern Clinics in Surgery

基　　金：国家自然科学基金(81972741,81672408);广东省自然科学基金(2020A1515010341);中大青年教师培养项目(19ykpy109);广东省自然科学基金博士科研启动项目(2018A030310227);中央高校基本科研业务费资助项目(18zxxt59);广东省医学科学技术研究基金项目(A2018012)。

摘　　要：目的运用TCGA数据库,分析组织金属蛋白酶抑制剂-1(TIMP1)在直肠癌中的表达情况,及与直肠癌预后的关系。分析与TIMP1高表达组与低表达组差异基因的分子功能及生物学功能。分析TIMP1与EFEMP1的关系,EFEMP1与直肠癌预后的关系。方法下载TCGA数据库中直肠癌相关数据,分析TIMP1在癌旁组织与直肠癌组织中的表达差异。分析不同临床分期患者的TIMP1表达水平。Kaplan-Meier生存曲线分析TIMP1表达量与直肠癌患者总体生存时间(OS)和无瘤生存时间(PFS)的关系。根据TIMP1表达水平,将直肠癌病人分为TIMP1高表达与低表达组,分析两组差异基因。对差异基因进行富集分析及通路分析,从而探索TIMP1相关基因的功能。寻找与TIMP1密切相关的基因,分析其与TIMP1的相关性,分析其与直肠癌预后的关系。结果与癌旁组织比较,TIMP1在直肠癌组织中呈高表达,Ⅰ期、Ⅱ期、Ⅲ期和Ⅳ期患者的TIMP1水平比对照组高。TIMP1表达水平越高,患者总体生存时间与无瘤生存时间越短,预后越差。基因富集结果显示,TIMP1高表达组与低表达组的差异基因,大多参与细胞黏附,维持细胞外基质稳定性等生物学过程。通路分析结果显示,差异基因在功能上与参与上皮-间质转化(EMT)的基因存在密切关联。其中含表皮生长因子的纤维蛋白样细胞外基质蛋白1(EFEMP1)基因与TIMP1呈正相关,EFEMP1表达越高,直肠癌患者总体生存时间和无瘤生存时间越短,预后越差。结论TIMP1在直肠癌中高表达,与预后呈负相关。TIMP1与EFEMP1呈正相关;EFEMP1基因在直肠癌中与预后呈负相关。Objective To analyze the expression of tissue inhibitor of metalloproteinases-1(TIMP1)in rectal cancer and its relationship with the prognosis of rectal cancer.To analyze the molecular and biological functions of different genes in the high-expression and low-expression groups of TIMP1.To analyze the relationship between TIMP1 and EFEMP1.To analyze the relationship between EFEMP1 and prognosis of rectal cancer.Methods Data related to rectal cancer in TCGA database were downloaded to analyze the expression of TIMP1 in adjacent normal tissues and rectal cancer tissues.The relationship between TIMP1 expression and prognosis of rectal cancer patients was analyzed by Kaplan-Meier curve.According to the expression level of TIMP1,rectal cancer patients were divided into groups with high expression of TIMP1 and low expression of TIMP1.The two groups were screened for different genes.Enrichment analysis and pathway analysis were carried out to explore the function of TIMP1 related genes.Genes closely related to TIMP1 were searched.Their correlation between the gene and TIMP1 was analyzed.The relationship between the gene and prognosis of rectal cancer was analyzed.Results Compared with adjacent normal tissues,TIMP1 was highly expressed in rectal cancer tissues.Patients with stageⅠ,Ⅱ,ⅢandⅣhad higher levels of TIMP1 than the control group.The higher the expression level of TIMP1,the shorter the overall survival time and the tumor-free survival time of the patients.Gene enrichment results showed that most of the different genes in the high-expression and low-expression groups of TIMP1 were involved in biological processes such as cell adhesion and maintenance of extracellular matrix stability.Pathway analysis showed that differential genes were functionally closely related to the epithelial-mesenchymal transition(EMT).Among them,the gene of Epidermal Growth factor-containing fibulin-like Extracellular Matrix Protein 1(EFEMP1)was positively correlated with TIMP1.The higher the expression of EFEMP1,the shorter the over

关 键 词：TCGA TIMP1 EFEMP1 EMT 直肠癌 预后 

分 类 号：R735.37[医药卫生—肿瘤]