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. 2016 Apr;141(1):95-100.
doi: 10.1016/j.ygyno.2016.02.023.

Molecular classification of high grade endometrioid and clear cell ovarian cancer using TCGA gene expression signatures

Boris Winterhoff  1 , Habib Hamidi  2 , Chen Wang  3 , Kimberly R Kalli  3 , Brooke L Fridley  4 , Judy Dering  2 , Hsiao-Wang Chen  2 , William A Cliby  5 , He-Jing Wang  6 , Sean Dowdy  5 , Bobbie S Gostout  5 , Gary L Keeney  5 , Ellen L Goode  3 , Gottfried E Konecny  7
Affiliations

Molecular classification of high grade endometrioid and clear cell ovarian cancer using TCGA gene expression signatures

Boris Winterhoff et al. Gynecol Oncol. 2016 Apr.

Abstract

Background: It is unclear whether the transcriptional subtypes of high grade serous ovarian cancer (HGSOC) apply to high grade clear cell (HGCCOC) or high grade endometrioid ovarian cancer (HGEOC). We aim to delineate transcriptional profiles of HGCCOCs and HGEOCs.

Methods: We used Agilent microarrays to determine gene expression profiles of 276 well annotated ovarian cancers (OCs) including 37 HGCCOCs and 66 HGEOCs. We excluded low grade OCs as these are known to be distinct molecular entities. We applied the prespecified TCGA and CLOVAR gene signatures using consensus non-negative matrix factorization (NMF).

Results: We confirm the presence of four TCGA transcriptional subtypes and their significant prognostic relevance (p<0.001) across all three histological subtypes (HGSOC, HGCCOC and HGEOCs). However, we also demonstrate that 22/37 (59%) HGCCOCs and 30/67 (45%) HGEOCs form 2 additional separate clusters with distinct gene signatures. Importantly, of the HGCCOC and HGEOCs that clustered separately 62% and 65% were early stage (FIGO I/II), respectively. These finding were confirmed using the reduced CLOVAR gene set for classification where most early stage HGCCOCs and HGEOCs formed a distinct cluster of their own. When restricting the analysis to the four TCGA signatures (ssGSEA or NMF with CLOVAR genes) most early stage HGCCOCs and HGEOC were assigned to the differentiated subtype.

Conclusions: Using transcriptional profiling the current study suggests that HGCCOCs and HGEOCs of advanced stage group together with HGSOCs. However, HGCCOCs and HGEOCs of early disease stages may have distinct transcriptional signatures similar to those seen in their low grade counterparts.

Keywords: Clear cell and high grade serous histologies; Endometrioid; Molecular subtypes; Ovarian cancer.

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Conflict of interest statement

The authors declare that there are no conflicts of interest.

Figures

Figure 1
Figure 1
Unsupervised clustering (non-negative matrix factorization) using 1500 TCGA genes depicting six clusters; overall survival according to transcriptional subtypes.
Figure 2
Figure 2
Unsupervised clustering (non-negative matrix factorization) using the 100 CLOVAR genes depicting five clusters; overall survival according to transcriptional subtypes.
Figure 3
Figure 3
Unsupervised clustering (non-negative matrix factorization) using the 100 CLOVAR genes depicting four clusters; overall survival according to transcriptional subtypes.
See this image and copyright information in PMC

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