Department of Infectious Diseases, Shunde Hospital, Southern Medical University, Shunde, China.
Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University, Shunde, China.
Cancer Sci. 2019 Sep;110(9):2905-2923. doi: 10.1111/cas.14138. Epub 2019 Aug 7.
The aim of the present study is to construct a competitive endogenous RNA (ceRNA) regulatory network by using differentially expressed long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in patients with hepatocellular carcinoma (HCC), and to construct a prognostic model for predicting overall survival (OS) of HCC patients. Differentially expressed lncRNAs, miRNAs, and mRNAs were explored between HCC tissues and normal liver tissues. A prognostic model was built for predicting OS of HCC patients and receiver operating characteristic curves were used to evaluate the performance of the prognostic model. There were 455 differentially expressed lncRNAs, 181 differentially expressed miRNAs, and 5035 differentially expressed mRNAs. A ceRNA regulatory network was constructed based on 43 lncRNAs, 37 miRNAs, and 105 mRNAs. Eight mRNA biomarkers (H2AFX, SQSTM1, ITM2A, PFKP, TPD52L1, ACSL4, STRN3, and CPEB3) were identified as independent risk factors by multivariate Cox regression and were used to develop a prognostic model for OS. The C-indexes in the model group were 0.776 (95% confidence interval [CI], 0.730-0.822), 0.745 (95% CI, 0.699-0.791), and 0.789 (95% CI, 0.743-0.835) for 1-, 3-, and 5-year OS, respectively. The current study revealed potential molecular biological regulation pathways and prognostic biomarkers by the ceRNA regulatory network. A prognostic model based on prognostic mRNAs in the ceRNA network might be helpful to predict the individual mortality risk for HCC patients. The individual mortality risk calculator can be used by visiting the following URL: https://zhangzhiqiao.shinyapps.io/Smart_cancer_predictive_system_HCC/.
本研究旨在构建肝细胞癌(HCC)患者差异表达的长链非编码 RNA(lncRNA)、微小 RNA(miRNA)和信使 RNA(mRNA)的竞争性内源性 RNA(ceRNA)调控网络,并构建预测 HCC 患者总生存期(OS)的预后模型。在 HCC 组织和正常肝组织之间探索差异表达的 lncRNA、miRNA 和 mRNA。为预测 HCC 患者的 OS 构建了预后模型,并使用接受者操作特征曲线评估了预后模型的性能。发现有 455 个差异表达的 lncRNA、181 个差异表达的 miRNA 和 5035 个差异表达的 mRNA。基于 43 个 lncRNA、37 个 miRNA 和 105 个 mRNA 构建了 ceRNA 调控网络。多变量 Cox 回归确定了 8 个 mRNA 生物标志物(H2AFX、SQSTM1、ITM2A、PFKP、TPD52L1、ACSL4、STRN3 和 CPEB3)为独立危险因素,并用于开发 OS 的预后模型。模型组的 C 指数分别为 0.776(95%可信区间[CI],0.730-0.822)、0.745(95%CI,0.699-0.791)和 0.789(95%CI,0.743-0.835),用于预测 1、3 和 5 年 OS。本研究通过 ceRNA 调控网络揭示了潜在的分子生物学调控途径和预后生物标志物。ceRNA 网络中预后 mRNA 构建的预后模型可能有助于预测 HCC 患者的个体死亡风险。个体死亡风险计算器可通过访问以下网址使用:https://zhangzhiqiao.shinyapps.io/Smart_cancer_predictive_system_HCC/。