title: Comprehensive Cross-Population Analysis of High-Grade Serous Ovarian Cancer Supports No More Than Three Subtypes.
abstract: Four gene expression subtypes of high-grade serous ovarian cancer (HGSC) have been previously described. In these early studies, a fraction of samples that did not fit well into the four subtype classifications were excluded. Therefore, we sought to systematically determine the concordance of transcriptomic HGSC subtypes across populations without removing any samples. We created a bioinformatics pipeline to independently cluster the five largest mRNA expression datasets using k-means and nonnegative matrix factorization (NMF). We summarized differential expression patterns to compare clusters across studies. While previous studies reported four subtypes, our cross-population comparison does not support four. Because these results contrast with previous reports, we attempted to reproduce analyses performed in those studies. Our results suggest that early results favoring four subtypes may have been driven by the inclusion of serous borderline tumors. In summary, our analysis suggests that either two or three, but not four, gene expression subtypes are most consistent across datasets.
authors.affiliation: Genomics and Computational Biology Graduate Program, University of Pennsylvania, Philadelphia, Pennsylvania 19103.|Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19103.
authors.forename: Gregory P
authors.identifier: 0000-0002-0503-9348
authors.initials: GP
authors.lastname: Way
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03766.
authors.forename: James
authors.initials: J
authors.lastname: Rudd
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Chen
authors.initials: C
authors.lastname: Wang
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
authors.forename: Habib
authors.initials: H
authors.lastname: Hamidi
authors.affiliation: Department of Biostatistics, University of Kansas Medical Center, Kansas City, Kansas 66160.
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.affiliation: Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, California 90095.
authors.forename: Gottfried E
authors.initials: GE
authors.lastname: Konecny
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55905.
authors.forename: Ellen L
authors.initials: EL
authors.lastname: Goode
authors.affiliation: Department of Systems Pharmacology and Translational Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania 19103 csgreene@upenn.edu jennifer.a.doherty@dartmouth.edu.|Department of Genetics, Geisel School of Medicine at Dartmouth, Hanover, New Hampshire 03755.
authors.forename: Casey S
authors.identifier: 0000-0001-8713-9213
authors.initials: CS
authors.lastname: Greene
authors.affiliation: Department of Epidemiology, Geisel School of Medicine at Dartmouth, Lebanon, New Hampshire 03766 csgreene@upenn.edu jennifer.a.doherty@dartmouth.edu.
authors.forename: Jennifer A
authors.identifier: 0000-0002-1454-8187
authors.initials: JA
authors.lastname: Doherty
mesh_terms: D016000:Cluster Analysis; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D030541:Databases, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D056726:Genetic Association Studies; D006801:Humans; D060787:Neoplasm Grading; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology*; D015203:Reproducibility of Results
keywords: molecular subtypes; ovarian cancer; reproducibility; unsupervised clustering