Huang Zi-Lin, Li Wang, Chen Qi-Feng, Wu Pei-Hong, Shen Lu-Jun
Department of Medical Imaging and Interventional Radiology, Sun Yat-sen University Cancer Center, Guangzhou 510060, Guangdong Province, China.
World J Gastrointest Oncol. 2019 Nov 15;11(11):983-997. doi: 10.4251/wjgo.v11.i11.983.
Hepatitis B virus, together with hepatitis C virus, has been recognized as the leading causes of hepatocellular carcinoma (HCC). Long non-coding RNAs (lncRNAs) have been suggested in increasing studies to be the potential prognostic factors for HCC. However, the role of combined application of lncRNAs in estimating overall survival (OS) for hepatitis virus positive HCC (VHCC) is uncertain.
To construct an lncRNA signature related to the OS of VHCC patients to enhance the accuracy of prognosis prediction.
The expression patterns of lncRNAs, as well as related clinical data were collected from 149 VHCC patients from The Cancer Genome Atlas database. The R package was adopted to obtain the differentially expressed lncRNAs (DElncRNAs). LncRNAs significantly associated with OS were screened by means of univariate Cox regression analysis, so as to construct a least absolute shrinkage and selection operator (LASSO) model. Subsequently, the constructed lncRNA signature was developed and validated. Afterwards, the prognostic nomogram was established, which combined the as-established lncRNA signature as well as the clinical features. Meanwhile, subgroup analysis stratified by the virus type was also performed. Finally, the above-mentioned lncRNAs were enriched to corresponding pathways according to the markedly co-expressed genes.
A total of 1420 DElncRNAs were identified, among which 406 were significant in univariate Cox regression analysis. LASSO regression confirmed 8 out of the 406 lncRNAs, including AC005722.2, AC107959.3, AL353803.1, AL589182.1, AP000844.2, AP002478.1, FLJ36000, and NPSR1-AS1. Then, the prognostic risk score was calculated. Our results displayed a significant association between the risk model and the OS of VHCC [hazard ratio = 1.94, 95% confidence interval (CI): 1.61-2.34, log-rank = 2e-10]. The inference tree suggested that the established lncRNA signature was useful in the risk stratification of VHCC. Furthermore, a nomogram was plotted, and the concordance index of internal validation was 0.763 (95%CI: 0.700-0.826). Moreover, the subgroup analysis regarding etiology confirmed this risk model. In addition, the Wnt signaling pathway, angiogenesis, the p53 pathway, and the PI3 kinase pathway were the remarkably enriched pathways.
An eight-lncRNA signature has been established to predict the prognosis for VHCC, which contributes to providing a novel foundation for the targeted therapy of VHCC.
乙型肝炎病毒与丙型肝炎病毒一起，已被公认为肝细胞癌（HCC）的主要病因。越来越多的研究表明，长链非编码RNA（lncRNAs）可能是HCC的潜在预后因素。然而，lncRNAs联合应用在评估肝炎病毒阳性HCC（VHCC）总生存期（OS）中的作用尚不确定。
构建与VHCC患者OS相关的lncRNA特征，以提高预后预测的准确性。
从癌症基因组图谱数据库中收集了149例VHCC患者的lncRNAs表达模式及相关临床数据。采用R包获取差异表达的lncRNAs（DElncRNAs）。通过单因素Cox回归分析筛选与OS显著相关的lncRNAs，构建最小绝对收缩和选择算子（LASSO）模型。随后，对构建的lncRNA特征进行开发和验证。之后，建立预后列线图，将已建立的lncRNA特征与临床特征相结合。同时，还进行了按病毒类型分层的亚组分析。最后，根据显著共表达基因将上述lncRNAs富集到相应通路。
共鉴定出1420个DElncRNAs，其中406个在单因素Cox回归分析中具有显著性。LASSO回归在406个lncRNAs中确认了8个，包括AC005722.2、AC107959.3、AL353803.1、AL589182.1、AP000844.2、AP002478.1、FLJ36000和NPSR1-AS1。然后，计算预后风险评分。我们的结果显示风险模型与VHCC的OS之间存在显著关联[风险比=1.94，95%置信区间（CI）：1.61-2.34，对数秩=2e-10]。推理树表明，建立的lncRNA特征有助于VHCC的风险分层。此外，绘制了列线图，内部验证的一致性指数为0.763（95%CI：0.700-0.826）。此外，病因亚组分析证实了该风险模型。此外，Wnt信号通路、血管生成、p53通路和PI3激酶通路是显著富集的通路。
已建立一个八lncRNA特征来预测VHCC的预后，这有助于为VHCC的靶向治疗提供新的基础。
