Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry

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 notewor...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Veröffentlicht in:Cell reports (Cambridge) 2018-02, Vol.22 (7), p.1875-1888
Hauptverfasser: Gonzalez, Veronica D., Samusik, Nikolay, Chen, Tiffany J., Savig, Erica S., Aghaeepour, Nima, Quigley, David A., Huang, Ying-Wen, Giangarrà, Valeria, Borowsky, Alexander D., Hubbard, Neil E., Chen, Shih-Yu, Han, Guojun, Ashworth, Alan, Kipps, Thomas J., Berek, Jonathan S., Nolan, Garry P., Fantl, Wendy J.
Format: Artikel
Sprache:eng
Schlagworte:
Online-Zugang:Volltext
Tags: Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
Beschreibung
Zusammenfassung: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. [Display omitted] •Cell types identified by CyTOF recur across newly diagnosed HGSOC tumors•Greater frequency of vimentin/cMyc/HE4 cells correlates with poor prognosis•A transitional EMT phenotype identified co-expressing E-cadherin and vimentin (EV)•In relapse patients, EV cells are positively correlated with a metastatic trajectory 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.
ISSN:2211-1247
2211-1247
DOI:10.1016/j.celrep.2018.01.053