A five-gene based risk score with high prognostic value in colorectal cancer.
A five-gene based risk score with high prognostic value in colorectal cancer.
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基于五基因的风险评分对结直肠癌具有较高的预后价值
DOI：
10.3892/ol.2017.7097
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发表时间：
2017-12
期刊：
影响因子：
2.9
通讯作者：
Zhang J
中科院分区：
文献类型：
--
作者：
Pan Y;Zhang H;Zhang M;Zhu J;Yu J;Wang B;Qiu J;Zhang J
结直肠癌（Colorectal cancer，CRC）是世界范围内最常见的恶性肿瘤之一。具有相似临床症状或处于相似病理阶段的患者的结局仍然不可预测。这种固有的临床多样性很可能是由于遗传异质性。本研究旨在建立一个基于基因谱的预测工具来评估患者的生存率。首先，利用三个基因表达综合数据集（GEO）（GSE 9348、GSE 44076和GSE 44861）来鉴定和验证CRC中的差异表达基因（DEG）。然后引入包含生存信息的GSE 14333数据集，以筛选和验证与乳腺癌相关的基因。在66个DEG中，本研究筛选出46个与患者总生存期密切相关的生物标志物。通过基因本体论和京都基因百科全书和基因组通路分析，证实这些基因参与多种生物学过程，与肿瘤的增殖、耐药和转移高度相关，从而进一步影响患者的生存。采用随机生存森林算法筛选出MET原癌基因、受体酪氨酸激酶、羧肽酶M、丝氨酸羟甲基转移酶2、鸟苷酸环化酶激活剂2B和钠电压门控通道α亚基9 5个最重要的基因，并进一步用多变量考克斯回归法拟合出线性风险评分公式。最后，本研究在三个独立的GEO数据集（GSE 14333，GSE 17536和GSE 29621）中测试和验证了该风险评分，并观察到具有高风险评分的患者具有较低的总生存率（P<0.05）。此外，该风险评分与其他预测因素（包括年龄和美国癌症联合委员会分期）相比，在模型中最显着，并且能够独立和直接地预测患者的生存。研究结果表明，这种生存相关的DEGs为基础的风险评分是一个强大的和准确的预后工具，并有望在临床环境中实施。
Colorectal cancer (CRC) is one of the most frequently occurring malignancies worldwide. The outcomes of patients with similar clinical symptoms or at similar pathological stages remain unpredictable. This inherent clinical diversity is most likely due to the genetic heterogeneity. The present study aimed to create a predicting tool to evaluate patient survival based on genetic profile. Firstly, three Gene Expression Omnibus (GEO) datasets (GSE9348, GSE44076 and GSE44861) were utilized to identify and validate differentially expressed genes (DEGs) in CRC. The GSE14333 dataset containing survival information was then introduced in order to screen and verify prognosis-associated genes. Of the 66 DEGs, the present study screened out 46 biomarkers closely associated to patient overall survival. By Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis, it was demonstrated that these genes participated in multiple biological processes which were highly associated with cancer proliferation, drug-resistance and metastasis, thus further affecting patient survival. The five most important genes, MET proto-oncogene, receptor tyrosine kinase, carboxypeptidase M, serine hydroxymethyltransferase 2, guanylate cyclase activator 2B and sodium voltage-gated channel a subunit 9 were selected by a random survival forests algorithm, and were further made up to a linear risk score formula by multivariable cox regression. Finally, the present study tested and verified this risk score within three independent GEO datasets (GSE14333, GSE17536 and GSE29621), and observed that patients with a high risk score had a lower overall survival (P<0.05). Furthermore, this risk score was the most significant compared with other predicting factors including age and American Joint Committee on Cancer stage, in the model, and was able to predict patient survival independently and directly. The findings suggest that this survival associated DEGs-based risk score is a powerful and accurate prognostic tool and is promisingly implemented in a clinical setting.
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影响因子：
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