title: Angiogenic mRNA and microRNA gene expression signature predicts a novel subtype of serous ovarian cancer.
abstract: 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.
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts, United States of America.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bentink
authors.forename: Benjamin
authors.initials: B
authors.lastname: Haibe-Kains
authors.forename: Thomas
authors.initials: T
authors.lastname: Risch
authors.forename: Jian-Bing
authors.initials: JB
authors.lastname: Fan
authors.forename: Michelle S
authors.initials: MS
authors.lastname: Hirsch
authors.forename: Kristina
authors.initials: K
authors.lastname: Holton
authors.forename: Renee
authors.initials: R
authors.lastname: Rubio
authors.forename: Craig
authors.initials: C
authors.lastname: April
authors.forename: Jing
authors.initials: J
authors.lastname: Chen
authors.forename: Eliza
authors.initials: E
authors.lastname: Wickham-Garcia
authors.forename: Joyce
authors.initials: J
authors.lastname: Liu
authors.forename: Aedin
authors.initials: A
authors.lastname: Culhane
authors.forename: Ronny
authors.initials: R
authors.lastname: Drapkin
authors.forename: John
authors.initials: J
authors.lastname: Quackenbush
authors.forename: Ursula A
authors.initials: UA
authors.lastname: Matulonis
mesh_terms: D000465:Algorithms; D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D002448:Cell Adhesion / Q000235:genetics; D005109:Extracellular Matrix / Q000235:genetics; D005260:Female; D020869:Gene Expression Profiling / Q000379:methods*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000032:analysis; D009389:Neovascularization, Pathologic / Q000235:genetics; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality; D012333:RNA, Messenger / Q000032:analysis; D015996:Survival Rate
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D035683:MicroRNAs; D012333:RNA, Messenger