Abstract
PurposeThis study further approaches the role of estrogen-related receptors (ERRs) in ovarian cancer. Protein expression of ERRα, ERRβ and ERRγ in ovarian cancer was assessed and was correlated with ovarian cancer markers, steroid hormone receptors and cancer-associated genes. Additionally, we examined to what extent expression of ERRs affects survival of ovarian cancer patients.MethodsFor this purpose, we established a tissue microarray from 208 ovarian cancer patients and performed immunohistochemical analyses of the mentioned proteins.ResultsERRα and ERRγ protein could be detected at different levels in more than 90% of all ovarian cancer tissues, whereas expression of ERRβ was observed in 82.2% of the cases. ERRα was found to positively correlate with ovarian cancer marker CEA (p < 0.005) and ERRγ correlated with ERα (p < 0.001). Univariate survival analyses revealed that ERRα expression did not affect overall (OS) or progression-free survival (PFS) of ovarian cancer patients. In contrast, higher expression of ERRβ in serous ovarian cancers was found to lead to a significantly decreased OS (p < 0.05). The strongest impact on survival was exhibited by ERRγ. Lower expression of this receptor in women with serous ovarian cancers indicated significantly increased OS compared to those with higher levels of ERRγ (p < 0.05). Multivariate survival analyses revealed ERRγ as an independent prognostic marker regarding OS of patients with serous ovarian cancer.ConclusionOur data demonstrating that ERR proteins are frequently expressed in ovarian cancer and high levels of ERRβ and ERRγ significantly decreased OS of serous ovarian cancer patients suggest that these proteins might be interesting therapy targets in this cancer entity.
Highlights
Ovarian cancer is the leading cause of death from a gynaecological malignancy in the developed world (Siegel et al 2018)
Given that there are only few data on the significance of estrogen-related receptors (ERRs) protein levels in ovarian cancer, in this study, we examined protein expression of ERRα, β and γ in 208 ovarian cancer samples, performed correlation analyses with ovarian cancer markers, steroid hormone receptors and other cancer-associated genes and performed Kaplan–Meier analyses to elucidate the effect of their expression levels on survival of ovarian cancer patients
Tissues from 208 Caucasian women with sporadic ovarian cancer were used in this study
Summary
Ovarian cancer is the leading cause of death from a gynaecological malignancy in the developed world (Siegel et al 2018). Estrogens activate growth in ovarian cancer cells via ERα which is often overexpressed in this cancer entity (Chan et al 2017; O’Donnell et al 2005). Both expression and specific activation of ERβ which is downregulated in most ovarian cancer cases, reduces ovarian cancer cell proliferation (Halon et al 2011; Schüler-Toprak et al 2017; Treeck et al 2007). Knowledge on the function and expression of estrogen-related receptors (ERRs) α, β and γ in ovarian cancer is sparse. They use estrogen response elements (EREs) and extended ERE half-sites termed ERR response elements (ERREs) (Ariazi and Jordan 2006). Thereby, among others, a vast number of different genes modulating metabolic processes are regulated and several different pathways are controlled (Ranhotra 2012)
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