Identification and validation of a new gene signature predicting prognosis of hepatocellular carcinoma patients by network analysis of stemness indices

Background: Stem cells play an important role in hepatocellular carcinoma (HCC). However, their precise effect on HCC tumorigenesis and progression remains unclear. The present study aimed to characterize stem cell-related gene expression in HCC.
Methods: The mRNA expression-based stemness index (mRNAsi) was used to analyze the clinical characteristics and prognosis of HCC patients. The weighted gene co-expression network analysis (WGCNA) was used to construct a gene co-expression network of 374 HCC patients. Finally, six genes were used to construct the prognosis signature.
Results: HCC patients had a higher mRNAsi score than healthy people, suggesting poor prognosis. Two gene modules highly related to mRNAsi were identified. Multivariate Cox analysis was carried out to establish a Cox proportional risk regression model. The risk score for each patient was the sum of the product of each gene expression and its coefficient. Survival analysis suggested that the low-risk group had a significantly better prognosis.
Conclusions: The established six-gene signature was able to predict patient prognosis accurately. This new signature should be verified in prospective studies in order to determine patient prognosis in clinical decision-making.

背景：干细胞在肝细胞癌（hepatocellular carcinoma, HCC）中发挥重要作用。然而，其对肝细胞癌发生与进展的确切作用仍未明确。本研究旨在阐明肝细胞癌中干细胞相关基因的表达特征。方法：采用基于mRNA表达的干细胞干性指数（mRNA expression-based stemness index, mRNAsi）分析肝细胞癌患者的临床特征与预后情况；通过加权基因共表达网络分析（weighted gene co-expression network analysis, WGCNA）构建374例肝细胞癌患者的基因共表达网络；最终筛选出6个基因以构建预后基因标签。结果：肝细胞癌患者的mRNAsi评分高于健康人群，提示预后不良；本研究鉴定出2个与mRNAsi高度相关的基因模块；通过多因素Cox分析构建Cox比例风险回归模型，每位患者的风险评分为各基因表达量与其系数的乘积之和；生存分析结果显示，低风险组患者的预后显著更优。结论：本研究构建的6基因标签可精准预测患者预后；该新型预后标签需在前瞻性研究中进一步验证，以期为临床决策中的患者预后评估提供依据。