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A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk

Title
A human lung tumor microenvironment interactome identifies clinically relevant cell-type cross-talk
Authors
Gentles, Andrew J.Hui, Angela Bik-YuFeng, WeiguoAzizi, ArmonNair, Ramesh, VBouchard, GinaKnowles, David A.Yu, AliceJeong, YoungtaeBejnood, AlborzForgo, ErnaVarma, SushamaXu, YueKuong, AmandaNair, Viswam S.West, Robvan de Rijn, MattHoang, Chuong D.Diehn, MaximilianPlevritis, Sylvia K.
DGIST Authors
Jeong, Youngtae
Issue Date
2020-05
Citation
Genome Biology, 21(1), 107
Type
Article
Article Type
Article
Keywords
TRANSCRIPTIONAL NETWORKPROGNOSTIC VALUEGROWTH-FACTORCANCERANGIOGENESISEXPRESSIONMUTATIONSINFILTRATIONFIBROBLASTSMODULATORS
ISSN
1474-760X
Abstract
Background: Tumors comprise a complex microenvironment of interacting malignant and stromal cell types. Much of our understanding of the tumor microenvironment comes from in vitro studies isolating the interactions between malignant cells and a single stromal cell type, often along a single pathway. Result: To develop a deeper understanding of the interactions between cells within human lung tumors, we perform RNA-seq profiling of flow-sorted malignant cells, endothelial cells, immune cells, fibroblasts, and bulk cells from freshly resected human primary non-small-cell lung tumors. We map the cell-specific differential expression of prognostically associated secreted factors and cell surface genes, and computationally reconstruct cross-talk between these cell types to generate a novel resource called the Lung Tumor Microenvironment Interactome (LTMI). Using this resource, we identify and validate a prognostically unfavorable influence of Gremlin-1 production by fibroblasts on proliferation of malignant lung adenocarcinoma cells. We also find a prognostically favorable association between infiltration of mast cells and less aggressive tumor cell behavior. Conclusion: These results illustrate the utility of the LTMI as a resource for generating hypotheses concerning tumor-microenvironment interactions that may have prognostic and therapeutic relevance. © 2020 The Author(s).
URI
http://hdl.handle.net/20.500.11750/12072
DOI
10.1186/s13059-020-02019-x
Publisher
BioMed Central Ltd.
Related Researcher
  • Author Jeong, Youngtae Lab of Stem Cell Biology & Cancer Precision Medicine
  • Research Interests Stem cells, Cancer, Precision medicine, Regenerative medicine, Nrf2, antioxidant
Files:
Collection:
Department of New BiologyLab of Stem Cell Biology & Cancer Precision Medicine1. Journal Articles


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