Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry
Veronica D. Gonzalez,
Nikolay Samusik,
Tiffany J. Chen,
Erica S. Savig,
Nima Aghaeepour,
David A. Quigley,
Ying-Wen Huang,
Valeria Giangarrà,
Alexander D. Borowsky,
Neil E. Hubbard,
Shih-Yu Chen,
Guojun Han,
Alan Ashworth,
Thomas J. Kipps,
Jonathan S. Berek,
Garry P. Nolan,
Wendy J. Fantl
Affiliations
Veronica D. Gonzalez
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Nikolay Samusik
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Tiffany J. Chen
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Erica S. Savig
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Nima Aghaeepour
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
David A. Quigley
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USA
Ying-Wen Huang
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Valeria Giangarrà
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Alexander D. Borowsky
Center for Comparative Medicine, University of California, Davis, Davis, CA 95616, USA; Department of Pathology and Laboratory Medicine, Comprehensive Cancer Center, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
Neil E. Hubbard
Center for Comparative Medicine, University of California, Davis, Davis, CA 95616, USA; Department of Pathology and Laboratory Medicine, Comprehensive Cancer Center, University of California, Davis School of Medicine, Sacramento, CA 95817, USA
Shih-Yu Chen
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Guojun Han
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Alan Ashworth
Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USA; Department of Medicine, University of California, San Francisco, 1450 Third Street, San Francisco, CA 94158, USA
Thomas J. Kipps
Moores Cancer Center, University of California, San Diego, La Jolla, CA 92093, USA
Jonathan S. Berek
Stanford Comprehensive Cancer Institute and Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA
Garry P. Nolan
Baxter Laboratory for Stem Cell Biology, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, CA 94305, USA
Wendy J. Fantl
Stanford Comprehensive Cancer Institute and Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA 94305, USA; Corresponding author
Summary: We have performed an in-depth single-cell phenotypic characterization of high-grade serous ovarian cancer (HGSOC) by multiparametric mass cytometry (CyTOF). Using a CyTOF antibody panel to interrogate features of HGSOC biology, combined with unsupervised computational analysis, we identified noteworthy cell types co-occurring across the tumors. In addition to a dominant cell subset, each tumor harbored rarer cell phenotypes. One such group co-expressed E-cadherin and vimentin (EV), suggesting their potential role in epithelial mesenchymal transition, which was substantiated by pairwise correlation analyses. Furthermore, tumors from patients with poorer outcome had an increased frequency of another rare cell type that co-expressed vimentin, HE4, and cMyc. These poorer-outcome tumors also populated more cell phenotypes, as quantified by Simpson’s diversity index. Thus, despite the recognized genomic complexity of the disease, the specific cell phenotypes uncovered here offer a focus for therapeutic intervention and disease monitoring.
