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胃癌预后9基因表达特征的鉴定与验证

Identification and validation of a prognostic 9-genes expression signature for gastric cancer.

作者信息

Wang Zhiqiang, Chen Gongxing, Wang Qilong, Lu Wei, Xu Meidong

机构信息

Endoscopy Center and Endoscopy Research Institute, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of General Surgery, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

出版信息

Oncotarget. 2017 May 10;8(43):73826-73836. doi: 10.18632/oncotarget.17764. eCollection 2017 Sep 26.

Abstract

Gastric cancer (GC) is a common malignant tumor with high incidence and mortality. Reasonable assessment of prognosis is essential to improve the outcomes of patients. In this study, we constructed and validated a prognostic gene model to evaluate the risks of GC patients. To identify the differentially expressed genes between GC patients and controls, we extracted Gene expression profiles of GC patients (N=432) from Gene Expression Omnibus database and then stable signature genes by using Robust likelihood-based modeling with 1000 iterations. Unsupervised hierarchical clustering of all samples was performed basing on the characteristics of gene expressions. Meanwhile, the differences between the clusters were analyzed by Kaplan Meier survival analysis. A 9-genes model was obtained (frequency = 999; p=1.333628e), including two negative impact factors ( and ) and 7 positive ones (). This model was verified in single factor survival analysis (p=0.004447558) and significant analysis with recurrence time (p=0.001474831) by using independent datasets from TCGA. The constructed 9-genes model was stable and effective, which might serve as prognostic signature to predict the survival of GC patients and monitor the long-term treatment of GC.

摘要

胃癌(GC)是一种发病率和死亡率都很高的常见恶性肿瘤。合理评估预后对于改善患者的治疗效果至关重要。在本研究中,我们构建并验证了一个预后基因模型,以评估GC患者的风险。为了确定GC患者与对照组之间差异表达的基因,我们从基因表达综合数据库中提取了GC患者(N = 432)的基因表达谱,然后通过基于稳健似然性的建模进行1000次迭代来确定稳定的特征基因。基于基因表达特征对所有样本进行无监督层次聚类。同时,通过Kaplan-Meier生存分析来分析聚类之间的差异。获得了一个由9个基因组成的模型(频率 = 999;p = 1.333628e),其中包括两个负性影响因子(和)以及7个正性影响因子()。使用来自TCGA的独立数据集,在单因素生存分析(p = 0.004447558)和复发时间的显著性分析(p = 0.001474831)中对该模型进行了验证。构建的9基因模型稳定且有效,可作为预测GC患者生存情况及监测GC长期治疗效果的预后标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0057/5650304/dec547d7b9c6/oncotarget-08-73826-g001.jpg

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