长链非编码RNA MALAT1在大肠癌中的表达及其临床意义:基于多基因表达数据库分析  

MALAT1 gene expression in colorectal cancer and its clinical significance: Data mining based on multiple gene expression databases

作　　者：倪雅懿 薛丽华[1] 张培 朱广博[1] Ya-Yi Ni;Li-Hua Xue;Pei Zhang;Guang-Bo Zhu(Clinical Laboratory,Tianjin People’s Hospital,Tianjin 300121,China)

机构地区：[1]天津市人民医院检验科

出　　处：《世界华人消化杂志》2019年第13期814-821,共8页World Chinese Journal of Digestology

摘　　要：背景结直肠癌(colorectal cancer, CRC)是临床中最为常见的消化系统恶性肿瘤,近年来长链非编码RNA(longchainnon-coding RNA, LncRNA)在CRC发生、发展及侵袭转移中发挥重要作用. MALAT1为新近发现的LncRNA,其在CRC中的作用及与患者预后的关系并不十分清楚.目的应用生物信息数据挖掘技术探讨LncRNA MALAT1在大肠癌中的差异表达及其临床意义.方法应用BioGPS数据库分析正常肠上皮中MALAT1的表达情况.在肿瘤芯片表达数据库Oncomine中荟萃分析大肠癌组织与正常肠上皮组织MALAT1的差异表达并分析MALAT1高、低表达与患者生存期是否存在相关性.在STRING数据库中应用蛋白相互作用网络分析与MALAT1相互作用及共表达的相关蛋白.结果MALAT1在正常大肠癌组织中的相对表达量较低.Oncomine数据库中,大肠癌差异表达的研究8项,其中6项在大肠癌中高表达, 2项低表达.比较大肠癌与对应正常组织的相关芯片数据为18个.大肠癌组织中MALAT1表达水平显著高于正常组织(P = 0.027).按结肠癌与直肠癌进亚组分析,结肠癌组织与正常组织MALAT1表达水平无统计学差异(P = 0.149),而直肠癌组织中MALAT1表达水平明显高于对应正常组织(P = 1.04 E-5).在Kaplan-Meier Plotter数据平台中分析MALAT1高、低表达组总生存期分别为41.93mo和52.2 mo,差异无统计学意义(HR = 0.64, 95%CI:0.29-1.39, P = 0.25). String数据库中分析与MALAT1可能相互作用的蛋白,结果显示MALAT1与TP53, SUZ12,CDK4, KDMA,等具有相互作用关系.共表达分析显示MALAT1与EZH2, TP53, SRSF1等基因具有共表达关系,提示这些基因在功能上可能具有相似性.结论大肠癌组织中MALAT1基因表达表达水平明显上调,但MALAT1表达水平与患者预后并无相关性.MALAT1与TP53, SUZ12, CDK4, KDMA蛋白相互作用,上述相互作用蛋白包括多梳蛋白家族,周期蛋白依赖性蛋白激酶等,与肿瘤的基因表达、转录调控及细胞分裂有关.BACKGROUND Colorectal cancer (CRC) is the most common malignant tumor of the digestive system. Long-chain noncoding RNAs (lncRNAs) play an important role in the occurrence, development, invasion and metastasis of CRC. MALAT1 is a newly discovered lncRNA, and its role in CRC and its relationship with prognosis are not completely clear. AIM To explore the differential expression of the lncRNA MALAT1 in CRC and its clinical significance by using bioinformatics data mining technology. METHODS BioGPS database was used to analyze the expression of MALAT1 in normal intestinal epithelium. Oncomine was used to meta-analyze the differential expression of MALAT1 in CRC tissue and normal intestinal epithelium tissue, and to analyze the difference of survival time between patients with high and low expression of MALAT1. Protein interaction network analysis was performed based on the STING database to analyze the proteins that potential interact with MALAT1. RESULTS The relative expression of MALAT1 in normal colorectal tissues was low. In Oncomine database, there were eight studies on differential expression of CRC, six of which suggested high expression of MALAT1 in CRC and two suggested low expression. The microarray data of 18 CRC and matched normal tissues were compared. The expression of MALAT1 in CRC tissues was significantly higher than that in normal tissues (P = 0.027). There was no significant difference in MALAT1 expression between colon cancer and normal tissues (P = 0.149), but the expression of MALAT1 in rectal cancer was significantly higher than that in normal tissues (P = 1.04 E-5). Kaplan- Meier Plotter analysis demonstrated that the overall survival time of the high and low MALAT1 expression functions. CONCLUSION The expression level of MALAT1 gene in CRC tissues is significantly up-regulated, but there is no correlation between MALAT1 expression and the prognosis of patients. MALAT1 interacts with TP53, SUZ12, CDK4, and KDMA proteins. These interacting proteins include Polycomb-group proteins, cyclin-depen

关 键 词：大肠癌 MALAT1基因 差异表达 预后 生物信息 数据挖掘 

分 类 号：R735.34[医药卫生—肿瘤]