title: Pooled Clustering of High-Grade Serous Ovarian Cancer Gene Expression Leads to Novel Consensus Subtypes Associated with Survival and Surgical Outcomes.
abstract: Purpose:Here we assess whether molecular subtyping identifies biological features of tumors that correlate with survival and surgical outcomes of high-grade serous ovarian cancer (HGSOC).Experimental Design:Consensus clustering of pooled mRNA expression data from over 2,000 HGSOC cases was used to define molecular subtypes of HGSOCs. Thisde novoclassification scheme was then applied to 381 Mayo Clinic HGSOC patients with detailed survival and surgical outcome information.Results:Five molecular subtypes of HGSOC were identified. In the pooled dataset, three subtypes were largely concordant with prior studies describing proliferative, mesenchymal, and immunoreactive tumors (concordance > 70%), and the group of tumors previously described as differentiated type was segregated into two new types, one of which (anti-mesenchymal) had downregulation of genes that were typically upregulated in the mesenchymal subtype. Molecular subtypes were significantly associated with overall survival (P< 0.001) and with rate of optimal surgical debulking (≤1 cm,P= 1.9E-4) in the pooled dataset. Among stage III-C or IV Mayo Clinic patients, molecular subtypes were also significantly associated with overall survival (P= 0.001), as well as rate of complete surgical debulking (no residual disease; 16% in mesenchymal tumors compared with >28% in other subtypes;P= 0.02).Conclusions:HGSOC tumors may be categorized into five molecular subtypes that associate with overall survival and the extent of residual disease following debulking surgery. Because mesenchymal tumors may have features that were associated with less favorable surgical outcome, molecular subtyping may have future utility in guiding neoadjuvant treatment decisions for women with HGSOC.Clin Cancer Res; 23(15); 4077-85. ©2017 AACR.
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Sebastian M
authors.initials: SM
authors.lastname: Armasu
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Kimberly R
authors.initials: KR
authors.lastname: Kalli
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Maurer
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ethan P
authors.initials: EP
authors.lastname: Heinzen
authors.affiliation: Department of Anatomic Pathology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Gary L
authors.initials: GL
authors.lastname: Keeney
authors.affiliation: Department of Gynecologic Surgery, Mayo Clinic, Rochester, Minnesota.
authors.forename: William A
authors.initials: WA
authors.lastname: Cliby
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota.
authors.forename: Ann L
authors.initials: AL
authors.lastname: Oberg
authors.affiliation: Department of Oncology, Mayo Clinic, Rochester, Minnesota.
authors.forename: Scott H
authors.initials: SH
authors.lastname: Kaufmann
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota. egoode@mayo.edu.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018284:Cystadenocarcinoma, Serous / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D018572:Disease-Free Survival; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D060787:Neoplasm Grading; D009363:Neoplasm Proteins / Q000235:genetics*; D018365:Neoplasm, Residual / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology* / Q000601:surgery; D011379:Prognosis; D016896:Treatment Outcome
chemical_list: D009363:Neoplasm Proteins