Single-cell RNA sequencing reveals gene expression signatures of breast cancer-associated endothelial cells

Zhengda Sun; Chih-Yang Wang; Devon A Lawson; Serena Kwek; Hugo Gonzalez Velozo; Mark Owyong; Ming-Derg Lai; Lawrence Fong; Mark Wilson; Hua Su; Zena Werb; Daniel L Cooke

doi:10.18632/oncotarget.23760

Single-cell RNA sequencing reveals gene expression signatures of breast cancer-associated endothelial cells

Oncotarget. 2017 Dec 29;9(13):10945-10961. doi: 10.18632/oncotarget.23760. eCollection 2018 Feb 16.

Authors

Zhengda Sun¹, Chih-Yang Wang^{2

3}, Devon A Lawson⁴, Serena Kwek⁵, Hugo Gonzalez Velozo², Mark Owyong², Ming-Derg Lai³, Lawrence Fong⁵, Mark Wilson¹, Hua Su⁶, Zena Werb², Daniel L Cooke¹

Affiliations

¹ Division of Neurointerventional Radiology, Department of Radiology and Biomedical Imaging, University of California, San Francisco, CA 94143, USA.
² Department of Anatomy, University of California, San Francisco, CA 94143, USA.
³ Department of Biochemistry and Molecular Biology, Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan 70101, Taiwan.
⁴ Department of Physiology and Biophysics, University of California, Irvine, CA 92697, USA.
⁵ Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, CA 94143, USA.
⁶ Center for Cerebrovascular Research, Department of Anesthesia and Perioperative Care, University of California, San Francisco, CA 94143, USA.

Abstract

Tumor endothelial cells (TEC) play an indispensible role in tumor growth and metastasis although much of the detailed mechanism still remains elusive. In this study we characterized and compared the global gene expression profiles of TECs and control ECs isolated from human breast cancerous tissues and reduction mammoplasty tissues respectively by single cell RNA sequencing (scRNA-seq). Based on the qualified scRNA-seq libraries that we made, we found that 1302 genes were differentially expressed between these two EC phenotypes. Both principal component analysis (PCA) and heat map-based hierarchical clustering separated the cancerous versus control ECs as two distinctive clusters, and MetaCore disease biomarker analysis indicated that these differentially expressed genes are highly correlated with breast neoplasm diseases. Gene Set Enrichment Analysis software (GSEA) enriched these genes to extracellular matrix (ECM) signal pathways and highlighted 127 ECM-associated genes. External validation verified some of these ECM-associated genes are not only generally overexpressed in various cancer tissues but also specifically overexpressed in colorectal cancer ECs and lymphoma ECs. In conclusion, our data demonstrated that ECM-associated genes play pivotal roles in breast cancer EC biology and some of them could serve as potential TEC biomarkers for various cancers.

Keywords: breast cancer; endothelial cell; extracellular matrix; single-cell RNA sequencing.

Abstract

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