A seven-gene signature predicts overall survival of patients with colorectal cancer.
A seven-gene signature predicts overall survival of patients with colorectal cancer.
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DOI：
10.18632/oncotarget.10982
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发表时间：
2017-11-10
期刊：
影响因子：
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通讯作者：
Zheng S
中科院分区：
文献类型：
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作者：
Chen H;Sun X;Ge W;Qian Y;Bai R;Zheng S
结直肠癌（CRC）是全球癌症死亡率的主要原因。基因表达谱可以帮助预测结直肠癌患者的预后。在以往的大多数研究中，疾病复发作为生存终点进行分析。因此，我们的目标是建立一个强大的基因签名预测总生存期（OS）的患者与CRC。使用Affyandem HG-U133 plus 2.0基因阵列分析了64例患者的新鲜冷冻CRC组织。通过单因素生存分析，发现6487个基因与我们队列中的OS相关。KEGG分析显示这些基因主要参与胞吞、轴突导向、剪接体、Wnt信号转导和泛素介导的蛋白水解等途径。一个七基因签名进一步选择了一个强大的基于似然生存建模方法。构建了7个基因标签（NHLRC 3，ZDHHC 21，PRR 14 L，CCBL 1，PTPRB，PNPO和PPIP 5 K2）的预后模型，并通过回归系数加权，将患者分为高风险组和低风险组。高风险组患者的OS显著差于低风险组患者。此外，发现所有七个基因在CRC组织中与邻近正常组织相比差异表达，表明它们在CRC发生和进展中的潜在作用。在另外两个独立队列中，这七个基因标记被进一步验证为CRC患者OS预测的独立预后标志物。简而言之，我们开发了一个强大的七基因签名，可以预测CRC患者的OS，为识别具有高死亡风险的CRC患者提供了新的见解。
Colorectal cancer (CRC) is a major cause of global cancer mortality. Gene expression profiles can help predict prognosis of patients with CRC. In most of previous studies, disease recurrence was analyzed as the survival endpoint. Thus we aim to build a robust gene signature for prediction of overall survival (OS) in patients with CRC. Fresh frozen CRC tissues from 64 patients were analyzed using Affymetrix HG-U133plus 2.0 gene arrays. By performing univariate survival analysis, 6487 genes were found to be associated with the OS in our cohort. KEGG analysis revealed that these genes were mainly involved in pathways such as endocytosis, axon guidance, spliceosome, Wnt signalling and ubiquitin mediated proteolysis. A seven-gene signature was further selected by a robust likelihood-based survival modelling approach. The prognostic model of seven-gene signature (NHLRC3, ZDHHC21, PRR14L, CCBL1, PTPRB, PNPO, and PPIP5K2) was constructed and weighted by regression coefficient, which divided patients into high- and low-risk groups. The OS for patients in high-risk group was significantly poorer compared with patients in low-risk group. Moreover, all seven genes were found to be differentially expressed in CRC tissues as compared with adjacent normal tissues, indicating their potential role in CRC initiation and progression. This seven-gene signature was further validated as an independent prognostic marker for OS prediction in patients with CRC in other two independent cohorts. In short, we developed a robust seven-gene signature that can predict the OS for CRC patients, providing new insights into identification of CRC patients with high risk of mortality.