Screening of prognosis-related enhancer RNAs and their corresponding target genes in patients with hepatocellular carcinoma and its prognostic significance
DOI:10.3872/j.issn.1007-385x.2021.09.008
- VernacularTitle:肝细胞癌患者预后相关增强子RNA和对应靶基因的筛选及其预后预测意义
- Author:
BAI Yi
1
;
WU Hao
2
;
ZHANG Yamin
1
Author Information
1. Department of Hepatobiliary Surgery, the First Central Hospital of Tianjin City, Tianjin 300192, China
2. Department of Hepatobiliary Surgery, the First Center Clinical College of Tianjin Medical University, Tianjin 300192, China
- Publication Type:Journal Article
- Keywords:
肝细胞癌;SMMC-7721细胞;生物信息学;预后;增强子RNA;靶基因
- From:
Chinese Journal of Cancer Biotherapy
2021;28(9):914-919
- CountryChina
- Language:Chinese
-
Abstract:
[摘 要] 目的: 筛选与肝细胞癌(hepatocellular carcinoma,HCC)预后相关的增强子RNA(enhancer RNA,eRNA)及其对应的靶基因,并探究其调控作用及功能。方法:通过UCSC数据库下载HCC的转录本数据和临床病例数据,提取eRNA及其预测的相应靶基因表达矩阵,用Kaplan-Meier和Spearman相关性分析方法筛选HCC预后相关的eRNA和靶基因,并采用最小化绝对收缩和选择算子回归分析及多因素Cox多元回归分析构建HCC预后风险评分模型。设计合成针对筛选所获关键eRNA AP003469.2的小干扰RNA并转染肝癌SMMC-7721细胞,采用RT-PCR方法验证敲减效率,qPCR法检测AP003469.2靶基因YWHAZ的表达水平,CCK-8法检测转染后SMMC-7721细胞的增殖情况。结果:筛选获得4个与预后相关基因,包括两个eRNA(AP003469.2和SPRY4-AS1)和两个靶基因(PPARGC1A和SLC2A1)(P<0.05),其中PPARGC1A高表达提示预后较好,AP003469.2、SPRY4-AS1和SLC2A1基因高表达则提示预后较差。基于4个基因构建的预后风险评分模型,第1、3和5年的AUC分别为0.730、0.699和0.679,提示模型具备良好的预测效能。在敲减AP003469.2后,SMMC-7721细胞中YWHAZ的表达无明显改变,且对细胞的增殖无影响。结论:基于生物信息学分析共筛选出4个关键基因,其中eRNA AP003469.2是HCC预后预测效能较高的标志物,其无促癌功能且对YWHAZ基因无调控作用。
- Full text:20210908.pdf