Stem Cell Translational Research Center, Tongji Hospital, Tongji University School of Medicine, Shanghai, China.
Department of Thoracic Surgery, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, China.
Thorac Cancer. 2019 May;10(5):1220-1228. doi: 10.1111/1759-7714.13072. Epub 2019 Apr 16.
Lung adenocarcinoma (LUAD) is a set of heterogeneous diseases with distinct genetic and transcriptomic characteristics. Since the introduction of the 2011 International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society histologic classification, increasing evidence has provided insights into genomic mutations and rearrangements among individual histologic subtypes of LUAD. However, how genotypic and phenotypic features of LUAD are interconnected is not well understood.
We obtained the genomic, transcriptomic, and clinical data sets of 488 LUAD patients from The Cancer Genome Atlas database. Advanced statistical models were used to disentangle the interactions between genetic mutations and expression profiles, and to assess the alterations and changes in expression of each histologic subtype. The prognostic impacts of genetic mutations, expression profiles, and clinicopathological features were integrated to predict the outcomes of LUAD patients.
From our data, one or more genetic mutations correlate with expression levels of 6054/18175 (33.3%) genes and explain 8-40% of observed variability in LUAD. The genetic mutations and expression profiles varied remarkably among the histologic subtypes of LUAD, which helped to explain the different prognostic impact based on subtype classification. Genomic, transcriptomic, and clinical data were all shown to have utility for predicting overall and recurrence-free survival, with the largest contribution from the transcriptome.
Our prediction model integrating genetic mutations, expression profiles, and clinicopathological features exhibited superior accuracy over the current tumor node metastasis staging system to prognosticate outcomes of patients with LUAD (overall survival 67% vs. 55%, recurrence-free survival 57% vs. 49%; P < 0.01).
肺腺癌（LUAD）是一组具有不同遗传和转录组特征的异质性疾病。自 2011 年国际肺癌研究协会/美国胸科学会/欧洲呼吸学会组织学分类引入以来，越来越多的证据为 LUAD 各个组织学亚型的基因组突变和重排提供了深入了解。然而，LUAD 的基因型和表型特征是如何相互关联的尚不清楚。
我们从癌症基因组图谱数据库中获得了 488 例 LUAD 患者的基因组、转录组和临床数据集。使用先进的统计模型来梳理遗传突变与表达谱之间的相互作用，并评估每个组织学亚型的改变和表达变化。整合遗传突变、表达谱和临床病理特征的预后影响，以预测 LUAD 患者的结局。
根据我们的数据，一个或多个基因突变与 6054/18175（33.3%）个基因的表达水平相关，可解释 LUAD 观察到的变异性的 8-40%。LUAD 的组织学亚型之间的遗传突变和表达谱差异显著，这有助于解释基于亚型分类的不同预后影响。基因组、转录组和临床数据均被证明可用于预测总生存期和无复发生存期，其中转录组的贡献最大。
我们整合遗传突变、表达谱和临床病理特征的预测模型在预测 LUAD 患者结局方面优于当前的肿瘤淋巴结转移分期系统（总生存期 67%比 55%，无复发生存期 57%比 49%；P<0.01）。
