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一种在膀胱癌中具有重大预后价值的八基因特征的构建与验证

Construction and validation of an eight-gene signature with great prognostic value in bladder cancer.

作者信息

Yan Xin, Fu Xun, Guo Zi-Xin, Liu Xiao-Ping, Liu Tong-Zu, Li Sheng

机构信息

Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

Department of Biological Repositories, Zhongnan Hospital of Wuhan University, Wuhan 430071, China.

出版信息

J Cancer. 2020 Jan 17;11(7):1768-1779. doi: 10.7150/jca.38741. eCollection 2020.

Abstract

Bladder cancer (BC) is one of the most common malignancies in urinary system with a common malignancy in urinary system with a high mortality and recurrence rate, so we attempt to construct a gene signature to predict the prognosis of BCs. We initially established a co-expression network by performing WGCNA analysis and further identified magenta module as key module (P = 8e-05, R2 = 0.4). Subsequently, we screened 12 genes associated with survival from the key module, which were selected to construct an eight-gene signature by establishing a LASSO Cox model. Moreover, we reckoned the risk score (RS) of each sample, through which we could divide samples into two groups (the high-risk and low-risk groups) and verify the signature, in the training set and 3 validation sets (internal test set, GSE13507and E-MTAB-4321). This signature could distinguish between the high- and low- risk patients well (survival analysis: P = 0.015; AUC: 0.61 at 1 year, 0.61 at 3 years and 0.61 at 5 years). In the validation sets, this signature also showed good performance, which was consistent with the training test. Furthermore, we plotted a nomogram to predict the possibility of the overall survival (OS) and three calibration curves to predict the effectiveness of the nomogram, which suggested good value and clinical utility of the nomogram. In conclusion, we established an eight-gene signature, which was probably effective in the prediction of prognosis of patients with BC.

摘要

膀胱癌(BC)是泌尿系统最常见的恶性肿瘤之一,具有高死亡率和复发率,因此我们试图构建一个基因特征来预测膀胱癌的预后。我们最初通过进行加权基因共表达网络分析(WGCNA)建立了一个共表达网络,并进一步将品红色模块确定为关键模块(P = 8e - 05,R2 = 0.4)。随后,我们从关键模块中筛选出12个与生存相关的基因,通过建立LASSO Cox模型从中选择构建了一个八基因特征。此外,我们计算了每个样本的风险评分(RS),据此将样本分为两组(高风险组和低风险组),并在训练集和3个验证集(内部测试集、GSE13507和E - MTAB - 4321)中验证该特征。这个特征能够很好地区分高风险和低风险患者(生存分析:P = 0.015;1年时AUC为0.61,3年时为0.61,5年时为0.61)。在验证集中,这个特征也表现出良好的性能,与训练测试结果一致。此外,我们绘制了一个列线图来预测总生存(OS)的可能性,并绘制了三条校准曲线来预测列线图的有效性,这表明列线图具有良好的价值和临床实用性。总之,我们建立了一个八基因特征,它可能对预测膀胱癌患者的预后有效。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a77/7052873/f55cad03abff/jcav11p1768g001.jpg

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