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 Hubbard, Shih Yu Chen, Guojun Han, Alan Ashworth, Thomas J. Kipps, Jonathan S. Berek, Garry P. Nolan, Wendy J. Fantl

Research output: Contribution to journalArticle

26 Scopus citations

Abstract

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. Although genetic and proteomic data from bulk-processed HGSOC tumors exist, critical information about rare cell subsets is lost. Using multiparametric CyTOF analysis of viable single cells from HGSOC tumors, Gonzalez et al. uncover cell types recurring across tumors with potential roles in metastasis and disease progression.

Original languageEnglish (US)
Pages (from-to)1875-1888
Number of pages14
JournalCell Reports
Volume22
Issue number7
DOIs
StatePublished - Feb 13 2018

Keywords

  • cMyc
  • CyTOF
  • HE4
  • heterogeneity
  • hierarchical clustering
  • high grade serious ovarian cancer
  • mass cytometry
  • phenotypic characterization
  • relapse
  • single cell

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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    Gonzalez, V. D., Samusik, N., Chen, T. J., Savig, E. S., Aghaeepour, N., Quigley, D. A., Huang, Y. W., Giangarrà, V., Borowsky, A. D., Hubbard, N., Chen, S. Y., Han, G., Ashworth, A., Kipps, T. J., Berek, J. S., Nolan, G. P., & Fantl, W. J. (2018). Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry. Cell Reports, 22(7), 1875-1888. https://doi.org/10.1016/j.celrep.2018.01.053