鉴定和验证肝细胞癌的预后四基因标记：整合的ceRNA网络分析

StephenW

Hepatology International

September 2019, Volume 13, Issue 5, pp 618–630 | Cite as
Identification and validation of a prognostic four-genes signature for hepatocellular carcinoma: integrated ceRNA network analysis

    Authors
    Authors and affiliations

    Yongcong YanYingjuan LuKai MaoMengyu ZhangHaohan LiuQianlei ZhouJianhong LinJianlong ZhangJie WangEmail authorZhiyu XiaoEmail author

    Yongcong Yan
        124
    Yingjuan Lu
        134
    Kai Mao
        124
    Mengyu Zhang
        5
    Haohan Liu
        124
    Qianlei Zhou
        124
    Jianhong Lin
        124
    Jianlong Zhang
        2
    Jie Wang
        2Email author
    Zhiyu Xiao
        2Email author

    1.Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
    2.Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
    3.Department of Oral and Maxillofacial Surgery, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
    4.RNA Biomedical Institute, Sun Yat-Sen Memorial HospitalSun Yat-Sen UniversityGuangzhouChina
    5.Department of Gastroenterology and Hepatology, The First Affiliated HospitalSun Yat-Sen UniversityGuangzhouChina

Open Access
Original Article
First Online: 18 July 2019

    1 Shares 474 Downloads 1 Citations

Abstract
Background

Hepatocellular carcinoma (HCC) is one of the most aggressive malignant tumors, with a poor long-term prognosis worldwide. The functional deregulations of global transcriptome were associated with the genesis and development of HCC, but lacks systematic research and validation.
Methods

A total of 519 postoperative HCC patients were included. We built an interactive and visual competing endogenous RNA network. The prognostic signature was established with the least absolute shrinkage and selection operator algorithm. Multivariate Cox regression analysis was used to screen for independent prognostic factors for HCC overall survival.
Results

In the training set, we identified a four-gene signature (PBK, CBX2, CLSPN, and CPEB3) and effectively predicted the overall survival. The survival times of patients in the high-score group were worse than those in the low-score group (p = 0.0004), and death was also more likely in the high-score group (HR 2.444, p < 0.001). The results were validated in internal validation set (p = 0.0057) and two external validation cohorts (HR 2.467 and 2.6). The signature (AUCs of 1, 2, 3 years were 0.716, 0.726, 0.714, respectively) showed high prognostic accuracy in the complete TCGA cohort.
Conclusions

In conclusion, we successfully built a more extensive ceRNA network for HCC and then identified a four-gene-based signature, enabling prediction of the overall survival of patients with HCC.
Keywords
Hepatocellular carcinoma Overall survival Competing endogenous RNA Least absolute shrinkage and selection operator Global transcriptome

StephenW

国际肝病学

2019年9月，第13卷，第5期，第618-630页|引用为
鉴定和验证肝细胞癌的预后四基因标记：整合的ceRNA网络分析

    作者
    作者和附属机构

    Yongcong YanYingjuan LuKai MaoMengyu Zhang Haohan LiuQianlei ZhouJianhong LinJianlong ZhangJie WangEmail authorhihiyu XiaoEmail author

    永聪燕
        124
    陆英娟
        134
    凯茂
        124
    孟梦章
        五
    刘浩汉
        124
    周千雷
        124
    林建红
        124
    张建龙
        2
    王杰
        2Email作者
    萧志宇
        2Email作者

    1.中山大学中山纪念医院广东省恶性肿瘤表观遗传学与基因调控重点实验室广州中国
    2.中山大学中山纪念医院肝胆外科，广州中国
    3.中山大学中山纪念医院口腔颌面外科，广州中国
    4.中山大学孙中山纪念医院生物医学研究所。广州中国
    5.中山大学附属第一医院消化内科，广州中国

开放存取
来源文章
首次在线：2019年7月18日

    1股474下载1引文

抽象
背景

肝细胞癌（HCC）是最具侵袭性的恶性肿瘤之一，其在世界范围内的长期预后较差。全球转录组的功能性失调与HCC的发生和发展有关，但缺乏系统的研究和验证。
方法

共纳入519例术后HCC患者。我们建立了一个互动和视觉竞争的内源RNA网络。使用最小绝对收缩和选择算子算法建立预后特征。多变量Cox回归分析用于筛选HCC总体存活的独立预后因素。
结果

在训练集中，我们确定了四基因特征（PBK，CBX2，CLSPN和CPEB3）并有效预测了总体存活率。高分组患者的生存时间低于低分组（p = 0.0004），高分组患者的死亡率也更高（HR 2.444，p <0.001）。结果在内部验证集（p = 0.0057）和两个外部验证队列（HR 2.467和2.6）中得到验证。签名（1年，2年，3年的AUC分别为0.716,0.726,0.714）在完整的TCGA群组中显示出高预后准确性。
结论

总之，我们成功地为HCC建立了更广泛的ceRNA网络，然后确定了基于四基因的特征，从而能够预测HCC患者的总体存活率。
关键词
肝细胞癌总生存竞争内源性RNA最小绝对收缩和选择操作符全局转录组

StephenW

https://link.springer.com/conten ... 072-019-09962-3.pdf