Bing Zhitong, Yao Yuxiang, Xiong Jie, Tian Jinhui, Guo Xiangqian, Li Xiuxia, Zhang Jingyun, Shi Xiue, Zhang Yanying, Yang Kehu
Evidence Based Medicine Center, School of Basic Medical Science of Lanzhou University, Lanzhou, China.
Key Laboratory of Evidence Based Medicine and Knowledge Translation of Gansu Province, Lanzhou, China.
Front Genet. 2019 Oct 11;10:931. doi: 10.3389/fgene.2019.00931. eCollection 2019.
Different analytical methods or models can often find completely different prognostic biomarkers for the same cancer. In the study of prognostic molecular biomarkers of ovarian cancer (OvCa), different studies have reported a variety of prognostic gene signatures. In the current study, based on geometric concepts, the linearity-clustering phase diagram with integrated P-value (LCP) method was used to comprehensively consider three indicators that are commonly employed to estimate the quality of a prognostic gene signature model. The three indicators, namely, concordance index, area under the curve, and level of the hazard ratio were determined calculation of the prognostic index of various gene signatures from different datasets. As evaluation objects, we selected 13 gene signature models (Cox regression model) and 16 OvCa genomic datasets (including gene expression information and follow-up data) from published studies. The results of LCP showed that three models were universal and better than other models. In addition, combining the three models into one model showed the best performance in all datasets by LCP calculation. The combination gene signature model provides a more reliable model and could be validated in various datasets of OvCa. Thus, our method and findings can provide more accurate prognostic biomarkers and effective reference for the precise clinical treatment of OvCa.
不同的分析方法或模型常常能为同一种癌症找到截然不同的预后生物标志物。在卵巢癌(OvCa)预后分子生物标志物的研究中,不同的研究报告了多种预后基因特征。在当前研究中,基于几何概念,采用带有整合P值的线性聚类相图(LCP)方法,全面考量了常用于评估预后基因特征模型质量的三个指标。这三个指标分别是一致性指数、曲线下面积和风险比水平,通过计算来自不同数据集的各种基因特征的预后指数来确定。作为评估对象,我们从已发表的研究中选取了13个基因特征模型(Cox回归模型)和16个OvCa基因组数据集(包括基因表达信息和随访数据)。LCP的结果表明,有三个模型具有通用性且优于其他模型。此外,将这三个模型组合成一个模型,经LCP计算在所有数据集中表现最佳。组合基因特征模型提供了一个更可靠的模型,并且可以在OvCa的各种数据集中进行验证。因此,我们的方法和研究结果能够为OvCa的精准临床治疗提供更准确的预后生物标志物和有效的参考。