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 language | English (US) |
|---|---|
| Pages (from-to) | 1875-1888 |
| Number of pages | 14 |
| Journal | Cell Reports |
| Volume | 22 |
| Issue number | 7 |
| DOIs | |
| State | Published - Feb 13 2018 |
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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
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 journal › Article
}
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 -