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

Boris Winterhoff, Habib Hamidi, Chen Wang, Kimberly R. Kalli, Brooke L. Fridley, Judy Dering, Hsiao Wang Chen, William Arthur Cliby, He Jing Wang, Sean Christopher Dowdy, Bobbie S. Gostout, Gary Keeney, Ellen L Goode, Gottfried E. Konecny

Research output: Contribution to journalArticle

13 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)95-100
Number of pages6
JournalGynecologic Oncology
Volume141
Issue number1
DOIs
StatePublished - Apr 1 2016

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Ovarian Neoplasms
Genes

Keywords

  • Clear cell and high grade serous histologies
  • Endometrioid
  • Molecular subtypes
  • Ovarian cancer

ASJC Scopus subject areas

  • Obstetrics and Gynecology
  • Oncology

Cite this

Molecular classification of high grade endometrioid and clear cell ovarian cancer using TCGA gene expression signatures. / Winterhoff, Boris; Hamidi, Habib; Wang, Chen; Kalli, Kimberly R.; Fridley, Brooke L.; Dering, Judy; Chen, Hsiao Wang; Cliby, William Arthur; Wang, He Jing; Dowdy, Sean Christopher; Gostout, Bobbie S.; Keeney, Gary; Goode, Ellen L; Konecny, Gottfried E.

In: Gynecologic Oncology, Vol. 141, No. 1, 01.04.2016, p. 95-100.

Research output: Contribution to journalArticle

Winterhoff, Boris ; Hamidi, Habib ; Wang, Chen ; Kalli, Kimberly R. ; Fridley, Brooke L. ; Dering, Judy ; Chen, Hsiao Wang ; Cliby, William Arthur ; Wang, He Jing ; Dowdy, Sean Christopher ; Gostout, Bobbie S. ; Keeney, Gary ; Goode, Ellen L ; Konecny, Gottfried E. / Molecular classification of high grade endometrioid and clear cell ovarian cancer using TCGA gene expression signatures. In: Gynecologic Oncology. 2016 ; Vol. 141, No. 1. pp. 95-100.
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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.",
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AU - Winterhoff, Boris

AU - Hamidi, Habib

AU - Wang, Chen

AU - Kalli, Kimberly R.

AU - Fridley, Brooke L.

AU - Dering, Judy

AU - Chen, Hsiao Wang

AU - Cliby, William Arthur

AU - Wang, He Jing

AU - Dowdy, Sean Christopher

AU - Gostout, Bobbie S.

AU - Keeney, Gary

AU - Goode, Ellen L

AU - Konecny, Gottfried E.

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N2 - 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.

AB - 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.

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KW - Ovarian cancer

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