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一种DNA修复基因特征的鉴定及预测前列腺癌无生化复发生存率的预后列线图的建立。

Identification of a DNA Repair Gene Signature and Establishment of a Prognostic Nomogram Predicting Biochemical-Recurrence-Free Survival of Prostate Cancer.

作者信息

Long Gongwei, Ouyang Wei, Zhang Yucong, Sun Guoliang, Gan Jiahua, Hu Zhiquan, Li Heng

机构信息

Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

Hubei Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.

出版信息

Front Mol Biosci. 2021 Mar 11;8:608369. doi: 10.3389/fmolb.2021.608369. eCollection 2021.

Abstract

The incidence of prostate cancer (PCa) is high and increasing worldwide. The prognosis of PCa is relatively good, but it is important to identify the patients with a high risk of biochemical recurrence (BCR) so that additional treatment could be applied. Level 3 mRNA expression and clinicopathological data were obtained from The Cancer Genome Atlas (TCGA) to serve as training data. The GSE84042 dataset was used as a validation set. Univariate Cox, lasso Cox, and stepwise multivariate Cox regression were applied to identify a DNA repair gene (DRG) signature. The performance of the DRG signature was assessed based on Kaplan-Meier curve, receiver operating characteristic (ROC), and Harrell's concordance index (C-index). Furtherly, a prognostic nomogram was established and evaluated likewise. A novel four DRG signature was established to predict BCR of PCa, which included POLM, NUDT15, AEN, and HELQ. The ROC and C index presented good performance in both training dataset and validation dataset. The patients were stratified by the signature into high- and low-risk groups with distinct BCR survival. Multivariate Cox analysis revealed that the DRG signature is an independent prognostic factor for PCa. Also, the DRG signature high-risk was related to a higher homologous recombination deficiency (HRD) score. The nomogram, incorporating the DRG signature and clinicopathological parameters, was able to predict the BCR with high efficiency and showed superior performance compared to models that consisted of only clinicopathological parameters. Our study identified a DRG signature and established a prognostic nomogram, which were reliable in predicting the BCR of PCa. This model could help with individualized treatment and medical decision making.

摘要

前列腺癌(PCa)在全球范围内的发病率很高且呈上升趋势。PCa的预后相对较好,但识别出具有高生化复发(BCR)风险的患者很重要,以便能够应用额外的治疗。从癌症基因组图谱(TCGA)获取3级mRNA表达和临床病理数据作为训练数据。GSE84042数据集用作验证集。应用单变量Cox、套索Cox和逐步多变量Cox回归来识别DNA修复基因(DRG)特征。基于Kaplan-Meier曲线、受试者工作特征(ROC)和Harrell一致性指数(C指数)评估DRG特征的性能。此外,建立了一个预后列线图并进行了同样的评估。建立了一种新的四个DRG特征来预测PCa的BCR,其中包括POLM、NUDT15、AEN和HELQ。ROC和C指数在训练数据集和验证数据集中均表现良好。根据该特征将患者分为具有不同BCR生存情况的高风险和低风险组。多变量Cox分析显示,DRG特征是PCa的独立预后因素。此外,DRG特征高风险与更高的同源重组缺陷(HRD)评分相关。纳入DRG特征和临床病理参数的列线图能够高效预测BCR,并且与仅由临床病理参数组成的模型相比表现更优。我们的研究识别出了一个DRG特征并建立了一个预后列线图,它们在预测PCa的BCR方面是可靠的。该模型有助于个体化治疗和医疗决策。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fa60/7991107/17c43ada21a1/fmolb-08-608369-g001.jpg

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