Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer

Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the seventh most fatal worldwide. Although ovarian cancer is notable for its initial sensitivity to platinum-based therapies, the vast majority of patients eventually develop recurrent cancer and succumb to increasin...

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Main Authors:	Bentink, Stefan, Haibe-Kains, Benjamin, Risch, Thomas, Fan, Jian-Bing, Hirsch, Michelle S., Holton, Kristina, Rubio, Renee, April, Craig, Chen, Jing, Wickham-Garcia, Eliza, Liu, Joyce, Culhane, Aedin, Drapkin, Ronny, Quackenbush, John, Matulonis, Ursula A.
Format:	Online
Language:	English
Published:	Public Library of Science 2012
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278409/

id	pubmed-3278409
recordtype	oai_dc
spelling	pubmed-32784092012-02-17 Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer Bentink, Stefan Haibe-Kains, Benjamin Risch, Thomas Fan, Jian-Bing Hirsch, Michelle S. Holton, Kristina Rubio, Renee April, Craig Chen, Jing Wickham-Garcia, Eliza Liu, Joyce Culhane, Aedin Drapkin, Ronny Quackenbush, John Matulonis, Ursula A. Research Article Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the seventh most fatal worldwide. Although ovarian cancer is notable for its initial sensitivity to platinum-based therapies, the vast majority of patients eventually develop recurrent cancer and succumb to increasingly platinum-resistant disease. Modern, targeted cancer drugs intervene in cell signaling, and identifying key disease mechanisms and pathways would greatly advance our treatment abilities. In order to shed light on the molecular diversity of ovarian cancer, we performed comprehensive transcriptional profiling on 129 advanced stage, high grade serous ovarian cancers. We implemented a, re-sampling based version of the ISIS class discovery algorithm (rISIS: robust ISIS) and applied it to the entire set of ovarian cancer transcriptional profiles. rISIS identified a previously undescribed patient stratification, further supported by micro-RNA expression profiles, and gene set enrichment analysis found strong biological support for the stratification by extracellular matrix, cell adhesion, and angiogenesis genes. The corresponding “angiogenesis signature” was validated in ten published independent ovarian cancer gene expression datasets and is significantly associated with overall survival. The subtypes we have defined are of potential translational interest as they may be relevant for identifying patients who may benefit from the addition of anti-angiogenic therapies that are now being tested in clinical trials. Public Library of Science 2012-02-13 /pmc/articles/PMC3278409/ /pubmed/22348002 http://dx.doi.org/10.1371/journal.pone.0030269 Text en Bentink 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	Bentink, Stefan Haibe-Kains, Benjamin Risch, Thomas Fan, Jian-Bing Hirsch, Michelle S. Holton, Kristina Rubio, Renee April, Craig Chen, Jing Wickham-Garcia, Eliza Liu, Joyce Culhane, Aedin Drapkin, Ronny Quackenbush, John Matulonis, Ursula A.
spellingShingle	Bentink, Stefan Haibe-Kains, Benjamin Risch, Thomas Fan, Jian-Bing Hirsch, Michelle S. Holton, Kristina Rubio, Renee April, Craig Chen, Jing Wickham-Garcia, Eliza Liu, Joyce Culhane, Aedin Drapkin, Ronny Quackenbush, John Matulonis, Ursula A. Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer
author_facet	Bentink, Stefan Haibe-Kains, Benjamin Risch, Thomas Fan, Jian-Bing Hirsch, Michelle S. Holton, Kristina Rubio, Renee April, Craig Chen, Jing Wickham-Garcia, Eliza Liu, Joyce Culhane, Aedin Drapkin, Ronny Quackenbush, John Matulonis, Ursula A.
author_sort	Bentink, Stefan
title	Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer
title_short	Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer
title_full	Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer
title_fullStr	Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer
title_full_unstemmed	Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer
title_sort	angiogenic mrna and microrna gene expression signature predicts a novel subtype of serous ovarian cancer
description	Ovarian cancer is the fifth leading cause of cancer death for women in the U.S. and the seventh most fatal worldwide. Although ovarian cancer is notable for its initial sensitivity to platinum-based therapies, the vast majority of patients eventually develop recurrent cancer and succumb to increasingly platinum-resistant disease. Modern, targeted cancer drugs intervene in cell signaling, and identifying key disease mechanisms and pathways would greatly advance our treatment abilities. In order to shed light on the molecular diversity of ovarian cancer, we performed comprehensive transcriptional profiling on 129 advanced stage, high grade serous ovarian cancers. We implemented a, re-sampling based version of the ISIS class discovery algorithm (rISIS: robust ISIS) and applied it to the entire set of ovarian cancer transcriptional profiles. rISIS identified a previously undescribed patient stratification, further supported by micro-RNA expression profiles, and gene set enrichment analysis found strong biological support for the stratification by extracellular matrix, cell adhesion, and angiogenesis genes. The corresponding “angiogenesis signature” was validated in ten published independent ovarian cancer gene expression datasets and is significantly associated with overall survival. The subtypes we have defined are of potential translational interest as they may be relevant for identifying patients who may benefit from the addition of anti-angiogenic therapies that are now being tested in clinical trials.
publisher	Public Library of Science
publishDate	2012
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3278409/
_version_	1611505702122029056

Angiogenic mRNA and microRNA Gene Expression Signature Predicts a Novel Subtype of Serous Ovarian Cancer

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