Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors
Abstract 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, muc...
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doaj-6aa7f79ba520452fabb8db53564d7c2d2020-11-25T00:02:45ZengBMCJournal of Ovarian Research1757-22152018-02-0111111010.1186/s13048-018-0389-9Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumorsAlicia Beeghly-Fadiel0Andrew J. Wilson1Spencer Keene2Meral El Ramahi3Shu Xu4Lawrence J. Marnett5Oluwole Fadare6Marta A. Crispens7Dineo Khabele8Department of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University Medical CenterDepartment of Obstetrics & Gynecology, Division of Gynecologic Oncology, Vanderbilt University Medical CenterDepartment of Medicine, Division of Epidemiology, Vanderbilt Epidemiology Center, Institute for Medicine and Public Health, Vanderbilt University Medical CenterDepartment of Obstetrics & Gynecology, Division of Gynecologic Oncology, Vanderbilt University Medical CenterDepartment of Biochemistry, Vanderbilt University Medical CenterDepartment of Biochemistry, Vanderbilt University Medical CenterDepartment of Pathology, School of Medicine, University of California, San DiegoVanderbilt-Ingram Cancer CenterDepartment of Obstetrics and Gynecology, Division of Gynecologic Oncology, The University of Kansas Medical CenterAbstract 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.http://link.springer.com/article/10.1186/s13048-018-0389-9CyclooxygenaseOvarian cancerTumor subtypeSurvival analysis |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Alicia Beeghly-Fadiel Andrew J. Wilson Spencer Keene Meral El Ramahi Shu Xu Lawrence J. Marnett Oluwole Fadare Marta A. Crispens Dineo Khabele |
spellingShingle |
Alicia Beeghly-Fadiel Andrew J. Wilson Spencer Keene Meral El Ramahi Shu Xu Lawrence J. Marnett Oluwole Fadare Marta A. Crispens Dineo Khabele Differential cyclooxygenase expression levels and survival associations in type I and type II ovarian tumors Journal of Ovarian Research Cyclooxygenase Ovarian cancer Tumor subtype Survival analysis |
author_facet |
Alicia Beeghly-Fadiel Andrew J. Wilson Spencer Keene Meral El Ramahi Shu Xu Lawrence J. Marnett Oluwole Fadare Marta A. Crispens Dineo Khabele |
author_sort |
Alicia Beeghly-Fadiel |
title |
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_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_sort |
differential cyclooxygenase expression levels and survival associations in type i and type ii ovarian tumors |
publisher |
BMC |
series |
Journal of Ovarian Research |
issn |
1757-2215 |
publishDate |
2018-02-01 |
description |
Abstract 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. |
topic |
Cyclooxygenase Ovarian cancer Tumor subtype Survival analysis |
url |
http://link.springer.com/article/10.1186/s13048-018-0389-9 |
work_keys_str_mv |
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