Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis
Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer ste...
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| Format: | Online |
| Language: | English |
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Public Library of Science
2013
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594231/ |
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pubmed-3594231 |
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pubmed-35942312013-03-27 Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis Schwede, Matthew Spentzos, Dimitrios Bentink, Stefan Hofmann, Oliver Haibe-Kains, Benjamin Harrington, David Quackenbush, John Culhane, Aedín C. Research Article Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable in the clinical management or treatment of ovarian cancer. Public Library of Science 2013-03-11 /pmc/articles/PMC3594231/ /pubmed/23536770 http://dx.doi.org/10.1371/journal.pone.0057799 Text en © 2013 Schwede et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited. |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Schwede, Matthew Spentzos, Dimitrios Bentink, Stefan Hofmann, Oliver Haibe-Kains, Benjamin Harrington, David Quackenbush, John Culhane, Aedín C. |
| spellingShingle |
Schwede, Matthew Spentzos, Dimitrios Bentink, Stefan Hofmann, Oliver Haibe-Kains, Benjamin Harrington, David Quackenbush, John Culhane, Aedín C. Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis |
| author_facet |
Schwede, Matthew Spentzos, Dimitrios Bentink, Stefan Hofmann, Oliver Haibe-Kains, Benjamin Harrington, David Quackenbush, John Culhane, Aedín C. |
| author_sort |
Schwede, Matthew |
| title |
Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis |
| title_short |
Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis |
| title_full |
Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis |
| title_fullStr |
Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis |
| title_full_unstemmed |
Stem Cell-Like Gene Expression in Ovarian Cancer Predicts Type II Subtype and Prognosis |
| title_sort |
stem cell-like gene expression in ovarian cancer predicts type ii subtype and prognosis |
| description |
Although ovarian cancer is often initially chemotherapy-sensitive, the vast majority of tumors eventually relapse and patients die of increasingly aggressive disease. Cancer stem cells are believed to have properties that allow them to survive therapy and may drive recurrent tumor growth. Cancer stem cells or cancer-initiating cells are a rare cell population and difficult to isolate experimentally. Genes that are expressed by stem cells may characterize a subset of less differentiated tumors and aid in prognostic classification of ovarian cancer. The purpose of this study was the genomic identification and characterization of a subtype of ovarian cancer that has stem cell-like gene expression. Using human and mouse gene signatures of embryonic, adult, or cancer stem cells, we performed an unsupervised bipartition class discovery on expression profiles from 145 serous ovarian tumors to identify a stem-like and more differentiated subgroup. Subtypes were reproducible and were further characterized in four independent, heterogeneous ovarian cancer datasets. We identified a stem-like subtype characterized by a 51-gene signature, which is significantly enriched in tumors with properties of Type II ovarian cancer; high grade, serous tumors, and poor survival. Conversely, the differentiated tumors share properties with Type I, including lower grade and mixed histological subtypes. The stem cell-like signature was prognostic within high-stage serous ovarian cancer, classifying a small subset of high-stage tumors with better prognosis, in the differentiated subtype. In multivariate models that adjusted for common clinical factors (including grade, stage, age), the subtype classification was still a significant predictor of relapse. The prognostic stem-like gene signature yields new insights into prognostic differences in ovarian cancer, provides a genomic context for defining Type I/II subtypes, and potential gene targets which following further validation may be valuable in the clinical management or treatment of ovarian cancer. |
| publisher |
Public Library of Science |
| publishDate |
2013 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3594231/ |
| _version_ |
1611961296408805376 |