Zhang Wenxia, Fu Qiang, Yao Kanyu
Department of Hepatobiliary Surgery, The Affiliated Hospital of Inner Mongolia Medical University, Hohhot, Inner Mongolia 010050, P.R. China.
Department of General Surgery, Erenhot Hospital, Erenhot, Inner Mongolia 011100, P.R. China.
Oncol Lett. 2020 Oct;20(4):48. doi: 10.3892/ol.2020.11911. Epub 2020 Jul 24.
Hepatocellular carcinoma (HCC) represents the fifth most common cause of cancer-associated mortality in men, and the seventh in women, worldwide. The aim of the present study was to identify a reliable and robust RNA-based risk score for the survival prediction of patients with hepatocellular carcinoma (HCC). Gene expression data from HCC and healthy control samples were obtained from The Cancer Genome Atlas to screen differentially expressed mRNAs and long non-coding RNAs (lncRNAs). Univariate and multivariate Cox proportional-hazards regression models and the LASSO algorithm for the Cox proportional-hazards model (LASSO Cox-PH model) were used to identify the prognostic mRNAs and lncRNAs among differentially expressed mRNAs (DEMs) and differentially expressed lncRNAs (DELs), respectively. Prognostic risk scores were generated based on the expression level or status of the prognostic lncRNAs and mRNAs, and the predictive abilities of these RNAs in TCGA and validation datasets were compared. Functional enrichment analyses were also performed. The results revealed a total of 154 downregulated and 625 upregulated mRNAs and 18 upregulated lncRNAs between tumor and control samples in TCGA dataset. A three-mRNA and a five-lncRNA expression signatures were identified using the LASSO Cox-PH model. Three-mRNA and five-lncRNA expression and status risk scores were generated. Using likelihood ratio P-values and area under the curve values from TCGA and the validation datasets, the three-mRNA status risk score was more accurate compared with the other risk scores in predicting the mortality of patients with HCC. The three identified mRNAs, including hepatitis A virus cellular receptor 1, MYCN proto-oncogene BHLH transcription factor and stratifin, were associated with the cell cycle and oocyte maturation pathways. Therefore, a three-mRNA status risk score may be valuable and robust for risk stratification of patients with HCC. The three-mRNA status risk score exhibited greater prognostic value compared with the lncRNA-based risk score.
肝细胞癌（HCC）是全球男性癌症相关死亡的第五大常见原因，女性为第七大常见原因。本研究的目的是确定一种可靠且强大的基于RNA的风险评分，用于预测肝细胞癌（HCC）患者的生存情况。从癌症基因组图谱获取肝癌和健康对照样本的基因表达数据，以筛选差异表达的mRNA和长链非编码RNA（lncRNA）。单变量和多变量Cox比例风险回归模型以及Cox比例风险模型的LASSO算法（LASSO Cox-PH模型）分别用于在差异表达的mRNA（DEM）和差异表达的lncRNA（DEL）中识别预后mRNA和lncRNA。基于预后lncRNA和mRNA的表达水平或状态生成预后风险评分，并比较这些RNA在TCGA和验证数据集中的预测能力。还进行了功能富集分析。结果显示，在TCGA数据集中，肿瘤样本和对照样本之间共有154个mRNA下调、625个mRNA上调以及18个lncRNA上调。使用LASSO Cox-PH模型确定了一个三mRNA和一个五lncRNA表达特征。生成了三mRNA和五lncRNA表达及状态风险评分。使用来自TCGA和验证数据集的似然比P值和曲线下面积值，在预测HCC患者死亡率方面，三mRNA状态风险评分比其他风险评分更准确。鉴定出的三个mRNA，包括甲型肝炎病毒细胞受体1、MYCN原癌基因BHLH转录因子和层粘连蛋白，与细胞周期和卵母细胞成熟途径相关。因此，三mRNA状态风险评分对于HCC患者的风险分层可能是有价值且可靠的。与基于lncRNA的风险评分相比，三mRNA状态风险评分具有更大的预后价值。
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