Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, Shaanxi Province, China.
Department of Clinical Laboratory, Liaocheng People's Hospital, Taishan Medical College, Liaocheng 252000, Shandong Province, China.
World J Gastroenterol. 2019 Apr 14;25(14):1715-1728. doi: 10.3748/wjg.v25.i14.1715.
Cellular senescence is a recognized barrier for progression of chronic liver diseases to hepatocellular carcinoma (HCC). The expression of a cluster of genes is altered in response to environmental factors during senescence. However, it is questionable whether these genes could serve as biomarkers for HCC patients.
To develop a signature of senescence-associated genes (SAGs) that predicts patients' overall survival (OS) to improve prognosis prediction of HCC.
SAGs were identified using two senescent cell models. Univariate COX regression analysis was performed to screen the candidate genes significantly associated with OS of HCC in a discovery cohort (GSE14520) for the least absolute shrinkage and selection operator modelling. Prognostic value of this seven-gene signature was evaluated using two independent cohorts retrieved from the GEO (GSE14520) and the Cancer Genome Atlas datasets, respectively. Time-dependent receiver operating characteristic (ROC) curve analysis was conducted to compare the predictive accuracy of the seven-SAG signature and serum α-fetoprotein (AFP).
A total of 42 SAGs were screened and seven of them, including , , , , , , and , were used to construct a prognostic formula. All seven genes were significantly downregulated in senescent cells and upregulated in HCC tissues. Survival analysis indicated that our seven-SAG signature was strongly associated with OS, especially in Asian populations, both in discovery and validation cohorts. Moreover, time-dependent ROC curve analysis suggested the seven-gene signature had a better predictive accuracy than serum AFP in predicting HCC patients' 1-, 3-, and 5-year OS.
We developed a seven-SAG signature, which could predict OS of Asian HCC patients. This risk model provides new clinical evidence for the accurate diagnosis and targeted treatment of HCC.
细胞衰老被认为是慢性肝脏疾病向肝细胞癌（HCC）进展的一个障碍。在衰老过程中，一组基因的表达会因环境因素而改变。然而，这些基因是否可以作为 HCC 患者的生物标志物还存在疑问。
开发一组与衰老相关的基因（SAGs）的特征，以预测患者的总生存期（OS），从而改善 HCC 的预后预测。
使用两种衰老细胞模型来鉴定 SAGs。使用最小绝对收缩和选择算子（LASSO）建模对发现队列（GSE14520）中与 HCC OS 显著相关的候选基因进行单因素 COX 回归分析。使用从 GEO（GSE14520）和癌症基因组图谱（TCGA）数据集分别检索到的两个独立队列来评估该七个基因特征的预后价值。进行时间依赖性接收器操作特征（ROC）曲线分析，以比较七个-SAG 特征和血清α-胎蛋白（AFP）的预测准确性。
共筛选出 42 个 SAG，其中 7 个，包括、、、、、、和，用于构建预后公式。所有七个基因在衰老细胞中均显著下调，在 HCC 组织中上调。生存分析表明，我们的七个-SAG 特征与 OS 密切相关，尤其是在亚洲人群中，无论是在发现队列还是验证队列中。此外，时间依赖性 ROC 曲线分析表明，七个基因特征在预测 HCC 患者 1、3 和 5 年 OS 方面的预测准确性优于血清 AFP。
我们开发了一个七个-SAG 特征，可以预测亚洲 HCC 患者的 OS。该风险模型为 HCC 的准确诊断和靶向治疗提供了新的临床证据。
