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Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors

BACKGROUND: High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 expression and its relation to survival is less clear. Here, we evaluated COX expression and associations with survival outcomes between type I (clear cell, mucinous, l...

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Autores principales: Beeghly-Fadiel, Alicia, Wilson, Andrew J., Keene, Spencer, El Ramahi, Meral, Xu, Shu, Marnett, Lawrence J., Fadare, Oluwole, Crispens, Marta A., Khabele, Dineo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828488/
https://www.ncbi.nlm.nih.gov/pubmed/29482584
http://dx.doi.org/10.1186/s13048-018-0389-9
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author Beeghly-Fadiel, Alicia
Wilson, Andrew J.
Keene, Spencer
El Ramahi, Meral
Xu, Shu
Marnett, Lawrence J.
Fadare, Oluwole
Crispens, Marta A.
Khabele, Dineo
author_facet Beeghly-Fadiel, Alicia
Wilson, Andrew J.
Keene, Spencer
El Ramahi, Meral
Xu, Shu
Marnett, Lawrence J.
Fadare, Oluwole
Crispens, Marta A.
Khabele, Dineo
author_sort Beeghly-Fadiel, Alicia
collection PubMed
description BACKGROUND: High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 expression and its relation to survival is less clear. Here, we evaluated COX expression and associations with survival outcomes between type I (clear cell, mucinous, low grade endometrioid and low grade serous) and type II (high grade serous and high grade endometrioid) ovarian tumors. METHODS: We developed and validated a new COX-1 antibody, and conducted immunohistochemical (IHC) staining for COX-1 and COX-2 on a tissue microarray (TMA) of 190 primary ovarian tumors. In addition to standard IHC scoring and H-scores to combine the percentage of positive cells and staining intensity, we also measured COX-1 and COX-2 mRNA expression by QPCR. High expression was defined as greater than or equal to median values. Clinical characteristics and disease outcomes were ascertained from medical records. Associations with disease-free survival (DFS) and overall survival (OS) were quantified by hazard ratios (HRs) and confidence intervals (CIs) from proportional hazards regression. RESULTS: Type I tumors had high COX-2 expression, while type II tumors had high COX-1 expression. In multivariable adjusted regression models, higher COX-1 mRNA expression was associated with shorter DFS (HR: 6.37, 95% CI: 1.84–22.01) and OS (HR: 2.26, 95% CI: 1.04–4.91), while higher H-scores for COX-2 expression were associated with shorter DFS (HR: 1.92, 95% CI: 1.06–3.49). Stratified analysis indicated that COX-2 was significantly associated with DFS among cases with Type II tumors (HR: 1.93, 95% CI: 1.06–3.53). CONCLUSIONS: These findings suggest that ovarian tumor type contributes to differences in COX expression levels and associations with survival. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13048-018-0389-9) contains supplementary material, which is available to authorized users.
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spelling pubmed-58284882018-03-01 Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors Beeghly-Fadiel, Alicia Wilson, Andrew J. Keene, Spencer El Ramahi, Meral Xu, Shu Marnett, Lawrence J. Fadare, Oluwole Crispens, Marta A. Khabele, Dineo J Ovarian Res Research BACKGROUND: High cyclooxygenase (COX)-2 expression in ovarian tumors has been associated with poor prognosis, but the role of COX-1 expression and its relation to survival is less clear. Here, we evaluated COX expression and associations with survival outcomes between type I (clear cell, mucinous, low grade endometrioid and low grade serous) and type II (high grade serous and high grade endometrioid) ovarian tumors. METHODS: We developed and validated a new COX-1 antibody, and conducted immunohistochemical (IHC) staining for COX-1 and COX-2 on a tissue microarray (TMA) of 190 primary ovarian tumors. In addition to standard IHC scoring and H-scores to combine the percentage of positive cells and staining intensity, we also measured COX-1 and COX-2 mRNA expression by QPCR. High expression was defined as greater than or equal to median values. Clinical characteristics and disease outcomes were ascertained from medical records. Associations with disease-free survival (DFS) and overall survival (OS) were quantified by hazard ratios (HRs) and confidence intervals (CIs) from proportional hazards regression. RESULTS: Type I tumors had high COX-2 expression, while type II tumors had high COX-1 expression. In multivariable adjusted regression models, higher COX-1 mRNA expression was associated with shorter DFS (HR: 6.37, 95% CI: 1.84–22.01) and OS (HR: 2.26, 95% CI: 1.04–4.91), while higher H-scores for COX-2 expression were associated with shorter DFS (HR: 1.92, 95% CI: 1.06–3.49). Stratified analysis indicated that COX-2 was significantly associated with DFS among cases with Type II tumors (HR: 1.93, 95% CI: 1.06–3.53). CONCLUSIONS: These findings suggest that ovarian tumor type contributes to differences in COX expression levels and associations with survival. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s13048-018-0389-9) contains supplementary material, which is available to authorized users. BioMed Central 2018-02-27 /pmc/articles/PMC5828488/ /pubmed/29482584 http://dx.doi.org/10.1186/s13048-018-0389-9 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
spellingShingle Research
Beeghly-Fadiel, Alicia
Wilson, Andrew J.
Keene, Spencer
El Ramahi, Meral
Xu, Shu
Marnett, Lawrence J.
Fadare, Oluwole
Crispens, Marta A.
Khabele, Dineo
Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors
title Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors
title_full Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors
title_fullStr Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors
title_full_unstemmed Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors
title_short Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors
title_sort differential cyclooxygenase expression levels and survival associations in type i and type ii ovarian tumors
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5828488/
https://www.ncbi.nlm.nih.gov/pubmed/29482584
http://dx.doi.org/10.1186/s13048-018-0389-9
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