Comprehensive Cross-Population Analysis of High-Grade Serous Ovarian Cancer Supports No More Than Three Subtypes.

Comprehensive Cross-Population Analysis of High-Grade Serous Ovarian Cancer Supports No More Than Three Subtypes.
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DOI:
10.1534/g3.116.033514
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发表时间:
2016-12-07
期刊:
G3 (Bethesda, Md.)
影响因子:
--
通讯作者:
Doherty JA
Doherty JA
中科院分区:
其他
文献类型:
--
作者:
Way GP;Rudd J;Wang C;Hamidi H;Fridley BL;Konecny GE;Goode EL;Greene CS;Doherty JA

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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.
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