@article {Way030239, author = {Gregory P. Way and James Rudd and Chen Wang and Habib Hamidi and Brooke L. Fridley and Gottfried Konecny and Ellen L. Goode and Casey S. Greene and Jennifer A. Doherty}, title = {High-grade serous ovarian cancer subtypes are similar across populations}, elocation-id = {030239}, year = {2015}, doi = {10.1101/030239}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Background Three to four gene expression-based subtypes of high-grade serous ovarian cancer (HGSC) have been previously reported. We sought to systematically determine the similarity of HGSC subtypes between populations.Methods We performed k-means clustering (k = 3 and k = 4) in five publicly-available HGSC mRNA expression datasets with \>130 tumors. Within each population, we summarized differential expression patterns for each cluster as moderated t statistic vectors using Significance Analysis of Microarrays. We calculated Pearson{\textquoteright}s correlations of these vectors to determine similarities and differences in expression patterns between clusters. We defined syn-clusters (SC) as sets of clusters that were strongly correlated across populations, and associated their expression patterns with biological pathways using geneset overrepresentation analyses.Results Across populations, for k = 3, moderated t score correlations for clusters 1, 2 and 3, respectively, ranged between 0.77-0.85, 0.80-0.90, and 0.65-0.77. For k = 4, correlations for clusters 1-4, respectively, ranged between 0.77-0.85, 0.83-0.89, 0.51-0.76, and 0.61-0.75. Within populations, comparing analogous clusters (k = 3 versus k = 4), correlations were high for clusters 1 and 2 (0.91-1.00), but were lower for cluster 3 (0.22-0.80). The results are similar using non-negative matrix factorization. SC1 corresponds to previously-reported mesenchymal-like, SC2 to proliferative-like, SC3 to immunoreactive-like, and SC4 to differentiated-like subtypes.Conclusions The ability to robustly identify correlated clusters across number of centroids, populations, and clustering methods provides strong evidence that at least three different HGSC subtypes exist. The mesenchymal-like and proliferative-like subtypes are remarkably consistent and could be uniquely targeted for treatment.}, URL = {https://www.biorxiv.org/content/early/2015/10/30/030239}, eprint = {https://www.biorxiv.org/content/early/2015/10/30/030239.full.pdf}, journal = {bioRxiv} }