title: Prognostic and therapeutic relevance of molecular subtypes in high-grade serous ovarian cancer.
abstract: Molecular classification of high-grade serous ovarian cancer (HGSOC) using transcriptional profiling has proven to be complex and difficult to validate across studies. We determined gene expression profiles of 174 well-annotated HGSOCs and demonstrate prognostic significance of the prespecified TCGA Network gene signatures. Furthermore, we confirm the presence of four HGSOC transcriptional subtypes using a de novo classification. Survival differed statistically significantly between de novo subtypes (log rank, P = .006) and was the best for the immunoreactive-like subtype, but statistically significantly worse for the proliferative- or mesenchymal-like subtypes (adjusted hazard ratio = 1.89, 95% confidence interval = 1.18 to 3.02, P = .008, and adjusted hazard ratio = 2.45, 95% confidence interval = 1.43 to 4.18, P = .001, respectively). More prognostic information was provided by the de novo than the TCGA classification (Likelihood Ratio tests, P = .003 and P = .04, respectively). All statistical tests were two-sided. These findings were replicated in an external data set of 185 HGSOCs and confirm the presence of four prognostically relevant molecular subtypes that have the potential to guide therapy decisions.
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Gottfried E
authors.initials: GE
authors.lastname: Konecny
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Habib
authors.initials: H
authors.lastname: Hamidi
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Boris
authors.initials: B
authors.lastname: Winterhoff
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kalli
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Judy
authors.initials: J
authors.lastname: Dering
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Charles
authors.initials: C
authors.lastname: Ginther
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Hsiao-Wang
authors.initials: HW
authors.lastname: Chen
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Sean
authors.initials: S
authors.lastname: Dowdy
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: William
authors.initials: W
authors.lastname: Cliby
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Bobbie
authors.initials: B
authors.lastname: Gostout
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Karl C
authors.initials: KC
authors.lastname: Podratz
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Gary
authors.initials: G
authors.lastname: Keeney
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: He-Jing
authors.initials: HJ
authors.lastname: Wang
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Lynn C
authors.initials: LC
authors.lastname: Hartmann
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Slamon
authors.affiliation: Division of Hematology-Oncology, Department of Medicine, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (GEK, HH, JD, CG, HWC, DJS); Department of Health Sciences Research (CW, ELG), Department of Gynecologic Surgery (BW, SD, WC, BG, KCP), Department of Medicine (KRK, LCH), and Department of Pathology (GK), Mayo Clinic, Rochester, MN; Department of Biostatistics, David Geffen School of Medicine, University of California Los Angeles, Los Angeles, CA (HJW).
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D018284:Cystadenocarcinoma, Serous / Q000737:chemistry / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D060787:Neoplasm Grading; D016017:Odds Ratio; D010051:Ovarian Neoplasms / Q000737:chemistry / Q000401:mortality* / Q000473:pathology / Q000628:therapy*; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D018401:Sample Size; D046888:Tissue Array Analysis; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor