肾透明细胞癌中长链非编码RNA的鉴定及验证  

Identification and validation of potential long non-coding RNA biomarkers in kidney renal clear cell carcinoma

作　　者：马慧敏 冯钢[2] MA Huimin;FENG Gang(Graduate School of Wannan Medical College,Wuhu 241002,China;Department of Clinical Laboratory,Yijishan Hospital,Wannan Medical College)

机构地区：[1]皖南医学院研究生院,安徽芜湖241002 [2]皖南医学院弋矶山医院检验科

出　　处：《沈阳医学院学报》2020年第4期313-320,共8页Journal of Shenyang Medical College

基　　金：安徽省自然科学基金(No.1508085MH157)。

摘　　要：目的:探讨长链非编码RNA(lncRNA)在肾透明细胞癌中的临床意义。方法:基于TCGA数据库中的肾透明细胞癌数据集分别鉴定异常表达的mRNA、miRNA和lncRNA,采用WGCNA确定与临床信息相关的关键lncRNA模块,根据ceRNA假说构建lncRNA-miRNA-mRNA ceRNA网络,在肾透明细胞癌的临床样本中验证了lncRNA在ceRNA网络中的临床意义。结果:包括109个lncRNA的蓝色模块与肾透明细胞癌的分期(cor=0.314,P<0.01)、转移(cor=0.224,P<0.01)和分级(cor=0.396,P<0.01)相关性最好,其中有15个lncRNA对肾透明细胞癌患者有较高的诊断价值。我们发现2个lncRNA、6个miRNA和39个mRNA在ceRNA网络中相互作用。生存分析表明,2个lncRNA(AL161937.2和LUC⁃AT1)是肾透明细胞癌患者的独立预后预测因子。对肾透明细胞癌的临床样本进行分析,AL161937.2和LUCAT1的高表达与肾透明细胞癌的晚期分期和高分级相关。结论:本研究通过lncRNA相关的ceRNA网络,为了解lncRNA在肾透明细胞癌中的作用提供了新的途径。LncRNA AL161937.2和LUCAT1可作为KIRC的诊断和预后标志物。Objective:To investigate the clinical significance of long non-coding RNA(lncRNA)in kidney renal clear cell carcinoma(KIRC).Methods:The aberrantly expressed mRNAs,miRNAs and lncRNAs were identified separately based on The Cancer Genome Atlas(TCGA)KIRC dataset.Weighted gene co-expression network analysis(WGCNA)was performed to determine the key lncRNA modules associated with clinical information.The clinical significances of lncRNAs in the key module were investigated.An lncRNA-miRNA-mRNA ceRNA network was constructed according to the ceRNA hypothesis.The clinical significances of lncRNAs in the ceRNA network were validated in clinical samples of KIRC.Results:One module(blue)was best associated with the pathologic stage(cor=0.314,P<0.01),pathologic metastasis(cor=0.224,P<0.01)and Grade(cor=0.396,P<0.01)in KIRC.Among 109 lncRNAs in blue module,15 lncRNAs had high diagnostic value for KIRC patients.Survival analysis indicated that 2 lncRNAs(AL161937.2 and LUCAT1)were independent prognostic predictors of KIRC patients.We found that 2 lncRNAs,6 miRNAs and 39 mRNAs interacted in the ceRNA network.High expressions of AL161937.2 and LUCAT1 were associated with advanced-stage and high-grade,which was validated in clinical samples of KIRC.Conclusions:This study provide a new approach to understand the function of lncRNAs in KIRC through lncRNA-associated ceRNA network.LncRNA AL161937.2 and LUCAT1 can be used as diagnostic and prognostic biomarkers in KIRC.

关 键 词：肾透明细胞癌 lncRNA ceRNA网络 

分 类 号：R737.11[医药卫生—肿瘤]