An integrated model of clinical information and gene expression for prediction of survival in ovarian cancer patients
An integrated model of clinical information and gene expression for prediction of survival in ovarian cancer patients
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用于预测卵巢癌患者生存的临床信息和基因表达的综合模型
DOI：
10.1016/j.trsl.2016.03.001
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发表时间：
2016-06-01
影响因子：
7.8
通讯作者：
Zeng, Xiaomin
中科院分区：
文献类型：
--
作者：
Yang, Rendong;Xiong, Jie;Zeng, Xiaomin
越来越多的证据表明，单靠临床因素并不足以预测卵巢癌（OvCa）患者的生存率，许多基因已被发现与OvCa预后相关。本研究的目的是开发一种整合临床信息和基因特征的模型，以预测诊断为OvCa的患者的生存期。我们构建了mRNA和microRNA表达谱，并从癌症基因组图谱中收集了552名OvCa患者和8名正常对照的相应临床数据。使用单变量考克斯回归，然后进行排列检验、弹性网络调节的考克斯回归和岭回归，我们生成了由2个临床变量、7个保护性mRNA、12个风险性mRNA和1个保护性microRNA组成的预后指数。临床-基因联合模型的受试者工作特征曲线下面积为0.756，大于单独临床模型（0.686）和单独基因模型（0.703）。高风险组中OvCa患者的总生存时间显著短于低风险组中的患者（风险比= 8.374，95%置信区间= 4.444-15.780，P = 4.90 x 10（-11），Wald检验）。基因签名的可靠性通过来自基因表达综合数据库的公共外部数据集确认。我们的结论是，我们已经确定了一个综合的临床和基因模型上级优于传统的单独的临床模型，在确定OvCa患者的生存预后。我们的研究结果可能对改善OvCa的临床管理有价值。
Accumulating evidence shows that clinical factors alone are not adequate for predicting the survival of patients with ovarian cancer (OvCa), and many genes have been found to be associated with OvCa prognosis. The objective of this study was to develop a model that integrates clinical information and a gene signature to predict the survival durations of patients diagnosed with OvCa. We constructed mRNA and microRNA expression profiles and gathered the corresponding clinical data of 552 OvCa patients and 8 normal controls from The Cancer Genome Atlas. Using univariate Cox regression followed by a permutation test, elastic net-regulated Cox regression, and ridge regression, we generated a prognosis index consisting of 2 clinical variables, 7 protective mRNAs, 12 risky mRNAs, and 1 protective microRNA. The area under the curve of the receiver operating characteristic of the integrated clinical-and-gene model was 0.756, larger than that of the clinical-alone model (0.686) or the gene-alone model (0.703). OvCa patients in the high-risk group had a significantly shorter overall survival time compared with patients in the low-risk group (hazard ratio = 8.374, 95% confidence interval = 4.444-15.780, P = 4.90 x 10(-11), by the Wald test). The reliability of the gene signature was confirmed by a public external data set from the Gene Expression Omnibus. Our conclusions that we have identified an integrated clinical-and-gene model superior to the traditional clinical-alone model in ascertaining the survival prognosis of patients with OvCa. Our findings may prove valuable for improving the clinical management of OvCa.