Wang Chao, Su Hai, Yang Lin, Huang Kun
Electrical and Computer Engineering, The Ohio State University, Columbus, Ohio, 43210, USA,
Pac Symp Biocomput. 2017;22:82-93. doi: 10.1142/9789813207813_0009.
Lung cancer is one of the most deadly cancers and lung adenocarcinoma (LUAD) is the most common histological type of lung cancer. However, LUAD is highly heterogeneous due to genetic difference as well as phenotypic differences such as cellular and tissue morphology. In this paper, we systematically examine the relationships between histological features and gene transcription. Specifically, we calculated 283 morphological features from histology images for 201 LUAD patients from TCGA project and identified the morphological feature with strong correlation with patient outcome. We then modeled the morphology feature using multiple co-expressed gene clusters using Lasso-regression. Many of the gene clusters are highly associated with genetic variations, specifically DNA copy number variations, implying that genetic variations play important roles in the development cancer morphology. As far as we know, our finding is the first to directly link the genetic variations and functional genomics to LUAD histology. These observations will lead to new insight on lung cancer development and potential new integrative biomarkers for prediction patient prognosis and response to treatments.
肺癌是最致命的癌症之一，肺腺癌（LUAD）是肺癌最常见的组织学类型。然而，由于基因差异以及细胞和组织形态等表型差异，LUAD具有高度异质性。在本文中，我们系统地研究了组织学特征与基因转录之间的关系。具体而言，我们从TCGA项目的201例LUAD患者的组织学图像中计算了283个形态学特征，并确定了与患者预后密切相关的形态学特征。然后，我们使用套索回归，通过多个共表达基因簇对形态学特征进行建模。许多基因簇与基因变异高度相关，特别是DNA拷贝数变异，这意味着基因变异在癌症形态发展中起重要作用。据我们所知，我们的发现首次将基因变异和功能基因组学与LUAD组织学直接联系起来。这些观察结果将为肺癌发展带来新的见解，并为预测患者预后和治疗反应提供潜在的新的综合生物标志物。
