RT Journal Article
SR Electronic
T1 Comprehensive cross-population analysis of high-grade serous ovarian cancer supports no more than three subtypes
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 030239
DO 10.1101/030239
A1 Gregory P. Way
A1 James Rudd
A1 Chen Wang
A1 Habib Hamidi
A1 Brooke L. Fridley
A1 Gottfried Konecny
A1 Ellen L. Goode
A1 Casey S. Greene
A1 Jennifer A. Doherty
YR 2016
UL http://biorxiv.org/content/early/2016/05/19/030239.abstract
AB Four gene expression subtypes of high-grade serous ovarian cancer (HGSC) have been described in several previous studies. In these studies, a fraction of samples that did not fit well into any of the four subtype classifications were excluded. Therefore, we sought to systematically determine the concordance of transcriptomic HGSC subtypes across populations without removing any “hard-to-classify” samples. We created a unified bioinformatics pipeline to independently cluster the five largest mRNA expression datasets using k-means and nonnegative matrix factorization (NMF). Within each population, we summarized differential expression patterns, which we used to compare clusters across studies. While previous studies reported four HGSC subtypes, our cross-population comparison does not support four subtypes. Because these results contrast with previous reports, we attempted to reproduce the analyses performed in those studies. Our results suggest that early results favoring four subtypes may have been driven, at least in part, by the inclusion of serous borderline tumors. In summary, our analysis suggests that either two or three, but not four, distinct gene expression subtypes are most consistent with the available HGSC data to date.CONFLICTS OF INTEREST The authors do not declare any conflicts of interest.OTHER PRESENTATIONS Aspects of this study were presented at the 2015 AACR Conference and the 2015 Rocky Mountain Bioinformatics Conference.AUTHORS’ CONTRIBUTIONS Study concept and design: GW, JR, CG, JD. Original data collection and processing: CW, HH, BF, GK, EG. Data analysis: GW, JR, CG, JD. Manuscript drafting and editing: GW, JR, CG, JD. All authors read, commented on, and approved the final manuscript.