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

19 Citations (Scopus)

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

Fingerprint

Tumors
Neoplasms
Ovarian Neoplasms
Vimentin
Phenotype
Single-Cell Analysis
Cadherins
Epithelial-Mesenchymal Transition
Proteomics
Disease Progression
Antibodies
Monitoring
Neoplasm Metastasis

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)

Cite this

Gonzalez, V. D., Samusik, N., Chen, T. J., Savig, E. S., Aghaeepour, N., Quigley, D. A., ... 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

Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry. / 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; Chen, Shih Yu; Han, Guojun; Ashworth, Alan; Kipps, Thomas J.; Berek, Jonathan S.; Nolan, Garry P.; Fantl, Wendy J.

In: Cell Reports, Vol. 22, No. 7, 13.02.2018, p. 1875-1888.

Research output: Contribution to journalArticle

Gonzalez, VD, Samusik, N, Chen, TJ, Savig, ES, Aghaeepour, N, Quigley, DA, Huang, YW, Giangarrà, V, Borowsky, AD, Hubbard, N, Chen, SY, Han, G, Ashworth, A, Kipps, TJ, Berek, JS, Nolan, GP & Fantl, WJ 2018, 'Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry', Cell Reports, vol. 22, no. 7, pp. 1875-1888. https://doi.org/10.1016/j.celrep.2018.01.053
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 ; Chen, Shih Yu ; Han, Guojun ; Ashworth, Alan ; Kipps, Thomas J. ; Berek, Jonathan S. ; Nolan, Garry P. ; Fantl, Wendy J. / Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry. In: Cell Reports. 2018 ; Vol. 22, No. 7. pp. 1875-1888.
@article{2b340cbf9bb648f28a7d41564ac03358,
title = "Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry",
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.",
keywords = "cMyc, CyTOF, HE4, heterogeneity, hierarchical clustering, high grade serious ovarian cancer, mass cytometry, phenotypic characterization, relapse, single cell",
author = "Gonzalez, {Veronica D.} and Nikolay Samusik and Chen, {Tiffany J.} and Savig, {Erica S.} and Nima Aghaeepour and Quigley, {David A.} and Huang, {Ying Wen} and Valeria Giangarr{\`a} and Borowsky, {Alexander D} and Neil Hubbard and Chen, {Shih Yu} and Guojun Han and Alan Ashworth and Kipps, {Thomas J.} and Berek, {Jonathan S.} and Nolan, {Garry P.} and Fantl, {Wendy J.}",
year = "2018",
month = "2",
day = "13",
doi = "10.1016/j.celrep.2018.01.053",
language = "English (US)",
volume = "22",
pages = "1875--1888",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "7",

}

TY - JOUR

T1 - Commonly Occurring Cell Subsets in High-Grade Serous Ovarian Tumors Identified by Single-Cell Mass Cytometry

AU - Gonzalez, Veronica D.

AU - Samusik, Nikolay

AU - Chen, Tiffany J.

AU - Savig, Erica S.

AU - Aghaeepour, Nima

AU - Quigley, David A.

AU - Huang, Ying Wen

AU - Giangarrà, Valeria

AU - Borowsky, Alexander D

AU - Hubbard, Neil

AU - Chen, Shih Yu

AU - Han, Guojun

AU - Ashworth, Alan

AU - Kipps, Thomas J.

AU - Berek, Jonathan S.

AU - Nolan, Garry P.

AU - Fantl, Wendy J.

PY - 2018/2/13

Y1 - 2018/2/13

N2 - 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.

AB - 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.

KW - cMyc

KW - CyTOF

KW - HE4

KW - heterogeneity

KW - hierarchical clustering

KW - high grade serious ovarian cancer

KW - mass cytometry

KW - phenotypic characterization

KW - relapse

KW - single cell

UR - http://www.scopus.com/inward/record.url?scp=85042014630&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85042014630&partnerID=8YFLogxK

U2 - 10.1016/j.celrep.2018.01.053

DO - 10.1016/j.celrep.2018.01.053

M3 - Article

C2 - 29444438

AN - SCOPUS:85042014630

VL - 22

SP - 1875

EP - 1888

JO - Cell Reports

JF - Cell Reports

SN - 2211-1247

IS - 7

ER -