Comprehensive analysis of mRNA-level and miRNA-level subpathway activities for identifying robust ovarian cancer prognostic signatures
Comprehensive analysis of mRNA-level and miRNA-level subpathway activities for identifying robust ovarian cancer prognostic signatures
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综合分析 mRNA 水平和 miRNA 水平的亚通路活性，以确定稳健的卵巢癌预后特征
DOI：
10.1111/jcmm.14968
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发表时间：
2020-01-19
影响因子：
5.3
通讯作者：
Zhang，Chunlong
中科院分区：
文献类型：
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作者：
Tian，Songyu;Mi，Wanqi;Zhang，Chunlong
卵巢癌（OvCa）是所有妇科癌症中死亡率最高的。大量基于 mRNA 或 miRNA 的特征被确定用于 OvCa 患者的预后。然而，OvCa 目前并未考虑功能级预后特征的综合分析。在本研究中，我们根据高通量表达谱和重建的子通路分别从 mRNA 和 miRNA 水平推断子通路活性。首先，计算两种肿瘤途径的活性，并使用多种肿瘤类型分析正常样本和肿瘤样本之间的差异。然后，我们根据 mRNA 和 miRNA 水平的表达谱计算了 OvCa 的子通路活性。此外，基于这些子通路活动矩阵，我们进行了引导分析以获得子训练集，并利用单变量方法来识别稳健的 OvCa 预后子通路。对这两个水平之间的子路径结果进行了全面比较。结果，我们观察到mRNA和miRNA水平之间的子通路互斥趋势，这表明结合mRNA-miRNA水平的必要性。最后，通过使用 ICGC 数据作为测试集，我们利用两种策略来验证 mRNA-miRNA 组合子通路特征的生存预测能力，并与个体水平的结果进行比较。经证实，我们的框架显示了用于识别 OvCa 稳健且有效的预后特征的应用程序，并且组合特征确实比单个特征表现出优势。在这项研究中，我们在 OvCa 预后的相关新型综合功能特征方面向前迈出了一步。
Ovarian cancer (OvCa) causes the highest mortality among all gynaecologic cancers. A large number of mRNA‐ or miRNA‐based signatures were identified for OvCa patient prognosis. However, the comprehensive analysis of function‐level prognostic signatures is currently not considered in OvCa. In the present study, we respectively inferred subpathway activities from mRNA and miRNA levels based on high‐throughput expression profiles and reconstructed subpathways. Firstly, the activities of two tumour pathways were calculated and the difference between normal and tumour samples were analysed using multiple tumour types. Then, we calculated subpathway activities for OvCa based on the expression profiles from both mRNA and miRNA levels. Furthermore, based on these subpathway activity matrices, we performed bootstrap analysis to obtain sub‐training sets and utilized univariate method to identify robust OvCa prognostic subpathways. A comprehensive comparison of subpathway results between these two levels was performed. As a result, we observed subpathway mutual exclusion trend between the levels of mRNA and miRNA, which indicated the necessary of combining mRNA‐miRNA levels. Finally, by using ICGC data as testing sets, we utilized two strategies to verify survival predictive power of the mRNA‐miRNA combined subpathway signatures and performed comparisons with results from individual levels. It was confirmed that our framework displayed application to identify robust and efficient prognostic signatures for OvCa, and the combined signatures indeed exhibited advantages over individual ones. In the study, we took a step forward in relevant novel integrated functional signatures for OvCa prognosis.