1] Graduate Program in Structural and Computational Biology and Molecular Biophysics, Baylor College of Medicine, Houston, Texas, USA. [2] Department of Bioinformatics and Computational Biology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA. [3].
1] Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts, USA. [2] Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3].
Nat Biotechnol. 2014 Jul;32(7):644-52. doi: 10.1038/nbt.2940. Epub 2014 Jun 22.
Molecular profiling of tumors promises to advance the clinical management of cancer, but the benefits of integrating molecular data with traditional clinical variables have not been systematically studied. Here we retrospectively predict patient survival using diverse molecular data (somatic copy-number alteration, DNA methylation and mRNA, microRNA and protein expression) from 953 samples of four cancer types from The Cancer Genome Atlas project. We find that incorporating molecular data with clinical variables yields statistically significantly improved predictions (FDR < 0.05) for three cancers but those quantitative gains were limited (2.2-23.9%). Additional analyses revealed little predictive power across tumor types except for one case. In clinically relevant genes, we identified 10,281 somatic alterations across 12 cancer types in 2,928 of 3,277 patients (89.4%), many of which would not be revealed in single-tumor analyses. Our study provides a starting point and resources, including an open-access model evaluation platform, for building reliable prognostic and therapeutic strategies that incorporate molecular data.
肿瘤的分子谱分析有望促进癌症的临床管理,但将分子数据与传统临床变量相结合的益处尚未得到系统研究。在这里,我们使用来自癌症基因组图谱计划的四种癌症类型的 953 个样本中的多种分子数据(体细胞拷贝数改变、DNA 甲基化和 mRNA、microRNA 和蛋白质表达),对患者的生存进行回顾性预测。我们发现,将分子数据与临床变量结合使用,可以显著提高三种癌症的预测效果(FDR<0.05),但这些定量增益是有限的(2.2-23.9%)。进一步的分析显示,除了一种情况外,肿瘤类型之间的预测能力很小。在临床相关基因中,我们在 3,277 名患者中的 2,928 名(89.4%)中发现了 12 种癌症类型的 10,281 种体细胞改变,其中许多改变在单个肿瘤分析中是不会被发现的。我们的研究为建立可靠的预后和治疗策略提供了一个起点和资源,包括一个开放获取的模型评估平台,该策略将整合分子数据。