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Computational staining of pathology images to study the tumor microenvironment in lung cancer.
Pubmed ID
31915129 (View this publication on the PubMed website)
Digital Object Identifier
Cancer Res. 2020 Jan 8

Wang S, Rong R, Yang DM, Fujimoto J, Yan S, Cai L, Yang L, Luo D, Behrens C, Parra ER, Yao B, Xu L, Wang T, Zhan X, Wistuba II, Minna J, Xie Y, Xiao G


The spatial organization of different types of cells in tumor tissues reveals important information about the tumor microenvironment (TME). In order to facilitate the study of cellular spatial organization and interactions, we developed Histology-based Digital (HD)-Staining, a deep learning-based computation model, to segment the nuclei of tumor, stroma, lymphocyte, macrophage, karyorrhexis and red blood cells from standard Hematoxylin and Eosin (H&E)-stained pathology images in lung adenocarcinoma (ADC). Using this tool, we identified and classified cell nuclei and extracted 48 cell spatial organization-related features that characterize the TME. Using these features, we developed a prognostic model from the National Lung Screening Trial dataset, and independently validated the model in The Cancer Genome Atlas (TCGA) lung ADC dataset, in which the predicted high-risk group showed significantly worse survival than the low-risk group (pv=0.001), with a hazard ratio of 2.23 [1.37-3.65] after adjusting for clinical variables. Furthermore, the image-derived TME features significantly correlated with the gene expression of biological pathways. For example, transcriptional activation of both the T-cell receptor (TCR) and programmed cell death protein 1 (PD1) pathways positively correlated with the density of detected lymphocytes in tumor tissues, while expression of the extracellular matrix organization pathway positively correlated with the density of stromal cells. In summary, we demonstrate that the spatial organization of different cell types is predictive of patient survival and associated with the gene expression of biological pathways.

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