Development and validation of a DNA repair gene signature for prognosis prediction in Colon Cancer
Development and validation of a DNA repair gene signature for prognosis prediction in Colon Cancer
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用于结肠癌预后预测的 DNA 修复基因特征的开发和验证
DOI：
10.7150/jca.46328
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发表时间：
2020-01-01
影响因子：
3.9
通讯作者：
Sheng, Weiqi
中科院分区：
文献类型：
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作者：
Wang, Xin;Tan, Cong;Sheng, Weiqi
DNA修复基因（DRGs）的异常表达可能与结肠癌的肿瘤进展和临床结局相关。在这里，我们的目的是建立一个DRGs签名，以确定结肠癌的重要预后DRGs。首先，通过基因集富集分析（GSEA）来证明背根神经节异常表达水平与肿瘤发生之间的关系。然后，从癌症基因组图谱（TCGA）结肠癌队列中随机选择295个病例，获得总共476个DRG用于检测候选生物标志物。用LASSO考克斯回归分析筛选11个基因建立预后模型。然后，使用内部验证数据集（TCGA队列中的其余125个病例）和外部验证数据集（从Gene Expression Omnibus数据集获得）来验证11个基因的预后模型和表达水平。进一步的分析揭示了独立的预后能力的预后模型与其他临床特征。受试者工作特征（ROC）曲线分析证实了预测模型的良好性能。此外，我们还提供了一个诺模图来解释11-DRG签名的临床应用。总之，我们提出了一个新开发的11-DRG签名作为一个实用的预测结肠癌患者的预后，这可以促进个性化的咨询和治疗。
Aberrant expression of DNA repair genes (DRGs) can be related to tumor progression and clinical outcomes in colon cancer. Here, we aimed to establish a DRGs signature to identify the vital prognostic DRGs in colon cancer. Firstly, gene set enrichment analysis (GSEA) was performed to demonstrate the association between abnormal expression level of DRGs and tumorigenesis. Then, a total of 476 DRGs were obtained for detecting candidate biomarkers in randomly selected 295 cases from The Cancer Genome Atlas (TCGA) colon cancer cohort. Eleven genes were screened by LASSO Cox regression analyses to develop the prognostic model. Then, the prognostic model and the expression levels of the eleven genes were validated using the internal validation dataset (the rest 125 cases in TCGA cohort) and an external validation dataset (obtained from Gene Expression Omnibus dataset). Further analysis revealed the independent prognostic capacity of the prognostic model in relation to other clinical characteristics. The receiver operating characteristic (ROC) curve analysis confirmed the good performance of the prognostic model. Furthermore, we provided a nomogram for interpreting the clinical application of the 11-DRG signature. In conclusion, we propose a newly developed 11-DRG signature as a practical prognostic predictor for patients with colon cancer, which can facilitate the individualized counselling and treatment.