Experimental and Translational Research Center, Beijing Friendship Hospital, Affiliated to the Capital University of Medical Sciences, Beijing, China.
Department of Blood Transfusion, Peking University People's Hospital, Beijing, China.
J Cell Physiol. 2019 Jul;234(7):11610-11619. doi: 10.1002/jcp.27818. Epub 2018 Nov 27.
The abnormal expression of microRNAs (miRNAs) or protein-coding genes (PCGs) have been found to be associated with the prognosis of hepatocellular carcinoma (HCC) patients. Using bioinformatics analysis methods including Cox's proportional hazards regression analysis, the random survival forest algorithm, Kaplan-Meier, and receiver operating characteristic (ROC) curve analysis, we mined the gene expression profiles of 469 HCC patients from The Cancer Genome Atlas (n = 379) and Gene Expression Omnibus (GSE14520; n = 90) public database. We selected a signature comprising one protein-coding gene (PCG; DNA polymerase μ) and three miRNAs (hsa-miR-149-5p, hsa-miR-424-5p, hsa-miR-579-5p) with highest accurate prediction (area under the ROC curve [AUC] = 0.72; n = 189) from the training data set. The signature stratified patients into high- and low-risk groups with significantly different survival (median 27.9 vs. 55.2 months, log-rank test, p < 0.001) in the training data set, and its risk stratification ability were validated in the test data set (median 47.4 vs. 84.4 months, log-rank test, p = 0.03) and an independent data set (median 31.0 vs. 46.0 months, log-rank test, p = 0.01). Multivariable Cox regression analysis showed that the signature was an independent prognostic factor. And the signature was proved to have a better survival prediction power than tumor-node-metastasis (TNM) stage (AUC = 0.72/0.64/0.62 vs. AUC = 0.65/0.61/0.61; p < 0.05). Moreover, we validated the expression of these prognostic genes from the PCG-miRNA signature in Huh-7 cell by real-time polymerase chain reaction. In conclusion, we found a signature that can predict survival of HCC patients and serve as a prognostic marker for HCC.
异常表达的 microRNAs（miRNAs）或蛋白质编码基因（PCGs）已被发现与肝细胞癌（HCC）患者的预后相关。我们使用包括 Cox 比例风险回归分析、随机生存森林算法、Kaplan-Meier 和接收者操作特征（ROC）曲线分析在内的生物信息学分析方法，从癌症基因组图谱（n = 379）和基因表达综合数据库（GSE14520；n = 90）的 469 名 HCC 患者的基因表达谱中挖掘数据。我们从训练数据集中选择了一个由一个蛋白质编码基因（PCG；DNA 聚合酶 μ）和三个 miRNA（hsa-miR-149-5p、hsa-miR-424-5p、hsa-miR-579-5p）组成的签名，该签名具有最高的预测准确性（ROC 曲线下面积[AUC] = 0.72；n = 189）。该签名在训练数据集中将患者分为高风险和低风险组，两组之间的生存情况有显著差异（中位生存时间 27.9 个月与 55.2 个月，对数秩检验，p < 0.001），并且在测试数据集（中位生存时间 47.4 个月与 84.4 个月，对数秩检验，p = 0.03）和独立数据集（中位生存时间 31.0 个月与 46.0 个月，对数秩检验，p = 0.01）中验证了其风险分层能力。多变量 Cox 回归分析表明，该签名是一个独立的预后因素。并且该签名在生存预测方面比肿瘤-淋巴结-转移（TNM）分期（AUC = 0.72/0.64/0.62 与 AUC = 0.65/0.61/0.61；p < 0.05）有更好的预测能力。此外，我们通过实时聚合酶链反应验证了来自 PCG-miRNA 签名的这些预后基因在 Huh-7 细胞中的表达。总之，我们发现了一个可以预测 HCC 患者生存情况的签名，可作为 HCC 的预后标志物。
