Expression signature distinguishing two tumour transcriptome classes associated with progression-free survival among rare histological types of epithelial ovarian cancer

Chen Wang, Boris J. Winterhoff, Kimberly R. Kalli, Matthew S Block, Sebastian M. Armasu, Melissa C. Larson, Hsiao Wang Chen, Gary Keeney, Lynn C. Hartmann, Vijayalakshmi Shridhar, Gottfried E. Konecny, Ellen L Goode, Brooke L. Fridley

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background:The mechanisms of recurrence have been under-studied in rare histologies of invasive epithelial ovarian cancer (EOC) (endometrioid, clear cell, mucinous, and low-grade serous). We hypothesised the existence of an expression signature predictive of outcome in the rarer histologies.Methods:In split discovery and validation analysis of 131 Mayo Clinic EOC cases, we used clustering to determine clinically relevant transcriptome classes using microarray gene expression measurements. The signature was validated in 967 EOC tumours (91 rare histological subtypes) with recurrence information.Results:We found two validated transcriptome classes associated with progression-free survival (PFS) in the Mayo Clinic EOC cases (P=8.24 × 10 -3). This signature was further validated in the public expression data sets involving the rare EOC histologies, where these two classes were also predictive of PFS (P=1.43 × 10 -3). In contrast, the signatures were not predictive of PFS in the high-grade serous EOC cases. Moreover, genes upregulated in Class-1 (with better outcome) were showed enrichment in steroid hormone biosynthesis (false discovery rate, FDR=0.005%) and WNT signalling pathway (FDR=1.46%); genes upregulated in Class-2 were enriched in cell cycle (FDR=0.86%) and toll-like receptor pathways (FDR=2.37%).Conclusions:These findings provide important biological insights into the rarer EOC histologies that may aid in the development of targeted treatment options for the rarer histologies.

Original languageEnglish (US)
Pages (from-to)1412-1420
Number of pages9
JournalBritish Journal of Cancer
Volume114
Issue number12
DOIs
StatePublished - Jun 14 2016

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Transcriptome
Disease-Free Survival
Histology
Neoplasms
Recurrence
Toll-Like Receptors
Ovarian epithelial cancer
Genes
Cluster Analysis
Cell Cycle
Steroids
Hormones
Gene Expression

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

Expression signature distinguishing two tumour transcriptome classes associated with progression-free survival among rare histological types of epithelial ovarian cancer. / Wang, Chen; Winterhoff, Boris J.; Kalli, Kimberly R.; Block, Matthew S; Armasu, Sebastian M.; Larson, Melissa C.; Chen, Hsiao Wang; Keeney, Gary; Hartmann, Lynn C.; Shridhar, Vijayalakshmi; Konecny, Gottfried E.; Goode, Ellen L; Fridley, Brooke L.

In: British Journal of Cancer, Vol. 114, No. 12, 14.06.2016, p. 1412-1420.

Research output: Contribution to journalArticle

Wang, Chen ; Winterhoff, Boris J. ; Kalli, Kimberly R. ; Block, Matthew S ; Armasu, Sebastian M. ; Larson, Melissa C. ; Chen, Hsiao Wang ; Keeney, Gary ; Hartmann, Lynn C. ; Shridhar, Vijayalakshmi ; Konecny, Gottfried E. ; Goode, Ellen L ; Fridley, Brooke L. / Expression signature distinguishing two tumour transcriptome classes associated with progression-free survival among rare histological types of epithelial ovarian cancer. In: British Journal of Cancer. 2016 ; Vol. 114, No. 12. pp. 1412-1420.
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abstract = "Background:The mechanisms of recurrence have been under-studied in rare histologies of invasive epithelial ovarian cancer (EOC) (endometrioid, clear cell, mucinous, and low-grade serous). We hypothesised the existence of an expression signature predictive of outcome in the rarer histologies.Methods:In split discovery and validation analysis of 131 Mayo Clinic EOC cases, we used clustering to determine clinically relevant transcriptome classes using microarray gene expression measurements. The signature was validated in 967 EOC tumours (91 rare histological subtypes) with recurrence information.Results:We found two validated transcriptome classes associated with progression-free survival (PFS) in the Mayo Clinic EOC cases (P=8.24 × 10 -3). This signature was further validated in the public expression data sets involving the rare EOC histologies, where these two classes were also predictive of PFS (P=1.43 × 10 -3). In contrast, the signatures were not predictive of PFS in the high-grade serous EOC cases. Moreover, genes upregulated in Class-1 (with better outcome) were showed enrichment in steroid hormone biosynthesis (false discovery rate, FDR=0.005{\%}) and WNT signalling pathway (FDR=1.46{\%}); genes upregulated in Class-2 were enriched in cell cycle (FDR=0.86{\%}) and toll-like receptor pathways (FDR=2.37{\%}).Conclusions:These findings provide important biological insights into the rarer EOC histologies that may aid in the development of targeted treatment options for the rarer histologies.",
author = "Chen Wang and Winterhoff, {Boris J.} and Kalli, {Kimberly R.} and Block, {Matthew S} and Armasu, {Sebastian M.} and Larson, {Melissa C.} and Chen, {Hsiao Wang} and Gary Keeney and Hartmann, {Lynn C.} and Vijayalakshmi Shridhar and Konecny, {Gottfried E.} and Goode, {Ellen L} and Fridley, {Brooke L.}",
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AU - Winterhoff, Boris J.

AU - Kalli, Kimberly R.

AU - Block, Matthew S

AU - Armasu, Sebastian M.

AU - Larson, Melissa C.

AU - Chen, Hsiao Wang

AU - Keeney, Gary

AU - Hartmann, Lynn C.

AU - Shridhar, Vijayalakshmi

AU - Konecny, Gottfried E.

AU - Goode, Ellen L

AU - Fridley, Brooke L.

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N2 - Background:The mechanisms of recurrence have been under-studied in rare histologies of invasive epithelial ovarian cancer (EOC) (endometrioid, clear cell, mucinous, and low-grade serous). We hypothesised the existence of an expression signature predictive of outcome in the rarer histologies.Methods:In split discovery and validation analysis of 131 Mayo Clinic EOC cases, we used clustering to determine clinically relevant transcriptome classes using microarray gene expression measurements. The signature was validated in 967 EOC tumours (91 rare histological subtypes) with recurrence information.Results:We found two validated transcriptome classes associated with progression-free survival (PFS) in the Mayo Clinic EOC cases (P=8.24 × 10 -3). This signature was further validated in the public expression data sets involving the rare EOC histologies, where these two classes were also predictive of PFS (P=1.43 × 10 -3). In contrast, the signatures were not predictive of PFS in the high-grade serous EOC cases. Moreover, genes upregulated in Class-1 (with better outcome) were showed enrichment in steroid hormone biosynthesis (false discovery rate, FDR=0.005%) and WNT signalling pathway (FDR=1.46%); genes upregulated in Class-2 were enriched in cell cycle (FDR=0.86%) and toll-like receptor pathways (FDR=2.37%).Conclusions:These findings provide important biological insights into the rarer EOC histologies that may aid in the development of targeted treatment options for the rarer histologies.

AB - Background:The mechanisms of recurrence have been under-studied in rare histologies of invasive epithelial ovarian cancer (EOC) (endometrioid, clear cell, mucinous, and low-grade serous). We hypothesised the existence of an expression signature predictive of outcome in the rarer histologies.Methods:In split discovery and validation analysis of 131 Mayo Clinic EOC cases, we used clustering to determine clinically relevant transcriptome classes using microarray gene expression measurements. The signature was validated in 967 EOC tumours (91 rare histological subtypes) with recurrence information.Results:We found two validated transcriptome classes associated with progression-free survival (PFS) in the Mayo Clinic EOC cases (P=8.24 × 10 -3). This signature was further validated in the public expression data sets involving the rare EOC histologies, where these two classes were also predictive of PFS (P=1.43 × 10 -3). In contrast, the signatures were not predictive of PFS in the high-grade serous EOC cases. Moreover, genes upregulated in Class-1 (with better outcome) were showed enrichment in steroid hormone biosynthesis (false discovery rate, FDR=0.005%) and WNT signalling pathway (FDR=1.46%); genes upregulated in Class-2 were enriched in cell cycle (FDR=0.86%) and toll-like receptor pathways (FDR=2.37%).Conclusions:These findings provide important biological insights into the rarer EOC histologies that may aid in the development of targeted treatment options for the rarer histologies.

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