A 4-gene prognostic signature predicting survival in hepatocellular carcinoma
A 4-gene prognostic signature predicting survival in hepatocellular carcinoma
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DOI：
10.1002/jcb.28187
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发表时间：
2019-06-01
影响因子：
4
通讯作者：
Fan, Bin
中科院分区：
文献类型：
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作者：
Chen, Peng-Fei;Li, Qing-He;Fan, Bin
目的建立独立的肝细胞癌（HCC）预后指标。方法以肝癌基因组图谱-肝细胞癌shcc基因表达谱和GSE14520基因表达谱分别作为发现集和检验集。差异表达基因（DEGs）在HCC组织和邻近的正常肝组织中被鉴定出来。进行单因素Cox比例风险回归分析，以确定deg与HCC患者生存相关。基于最小绝对收缩和选择算子Cox惩罚回归模型构建了一个基于4基因的签名。对签名的预测值进行了分析和验证。结果HCC与邻近肝组织间共检出263个deg。单因素生存分析发现90个基因与HCC患者总生存期（OS）有显著相关性，其中4个非零系数基因（KPNA2、CDC20、SPP1、TOP2A）被用来构建预后标志。4基因标记与发现组HCC患者的年龄（P=0.046）、分级（P=0.022）、T分期（P=0.023）显著相关，与TNM分期（P=0.033）、血清甲胎蛋白水平（P=0.034）显著相关。在发现组和试验组中，4基因低危组患者的OS和无复发生存期（RFS）均优于高危组。同时，在发现和测试集中，4基因标记是OS和RFS的独立预后因素。结论：我们开发了一个基于4基因的特征，这可能是HCC患者预后的一个候选因素。
ObjectiveTo develop an independent prognostic signature for patients with hepatocellular carcinoma (HCC).MethodsHCC gene expression profile the cancer genome atlas-liver hepatocellular carcinoma and GSE14520 were used as discovery and test set, respectively. Differentially expressed genes (DEGs) were identified between HCC tissues and adjacent normal liver tissues. Univariate Cox proportional hazards regression analysis was performed to identify DEGs correlated with survival of HCC patients. A 4-gene-based signature was constructed based on a least absolute shrinkage and selection operator Cox penalized regression model. The predictive value of the signature was analyzed and validated.ResultsTwo hundred sixty-three DEGs were identified between HCC and adjacent liver tissues. After univariate survival analysis, 90 DEGs were found to be significantly correlated with the overall survival (OS) of HCC patients, of which 4 genes (KPNA2, CDC20, SPP1, and TOP2A) with non-zero coefficient were used to construct a prognostic signature. The 4-gene signature was significantly associated with the age (P=0.046), grade (P=0.022), and T stage (P=0.023) of HCC patients in the discovery set and it also significantly associated with TNM stage (P=0.033), and serum alpha-fetoprotein lever (P=0.034). Patients in the 4-gene low-risk group were associated with better OS and recurrence-free survival (RFS) than those in the high-risk group in the discovery and test set. Meanwhile, the 4-gene signature is an independent prognostic factor regarding OS and RFS in the discovery and test set.ConclusionWe developed a 4-gene-based signature, which could be a candidate prognostic factor for patients with HCC.