Survival Is Related to Estrogen Signal Transduction Pathway Activity in Postmenopausal Women Diagnosed with High-Grade Serous Ovarian Carcinoma

Autor: Yvonne Wesseling-Rozendaal, Marjolein H.F.M. Lentjes-Beer, Jurgen M.J. Piek, Joanne A. de Hullu, Ruud L.M. Bekkers, Caroline Vos, Anja van de Stolpe, Steven L. Bosch, Laura A.M. van Lieshout, Meggy P.M. Ottenheijm, Leon F.A.G. Massuger, Phyllis van der Ploeg, Annelen Meriaan
Přispěvatelé: RS: GROW - R2 - Basic and Translational Cancer Biology, Obstetrie & Gynaecologie
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cancers
Volume 13
Issue 20
Cancers, 13(20):5101. Multidisciplinary Digital Publishing Institute (MDPI)
Cancers, Vol 13, Iss 5101, p 5101 (2021)
Cancers, 13
Cancers, 13, 20
ISSN: 2072-6694
DOI: 10.3390/cancers13205101
Popis: High-grade serous ovarian carcinoma (HGSC), the most common subtype of ovarian cancer, has a high mortality rate. Although there are some factors associated with survival, such as stage of disease, there are remarkable differences in survival among women diagnosed with advanced stage disease. In this study, we investigate possible relations between survival and signal transduction pathway (STP) activity. We assessed the functional activity of the androgen receptor (AR), estrogen receptor (ER), phosphoinositide-3-kinase (PI3K), Hedgehog (HH), transforming growth factor beta (TGF-β) and canonical wingless-type MMTV integration site (Wnt) pathway in 85 primary tumor samples of patients with FIGO stage IIIC to IVB HGSC and disease-free survival (DFS) below 12 (n = 52) or over 24 months (n = 33). There were no significant differences in median pathway activity between patients with a short and long DFS. In univariate Cox proportional hazards analysis, ER pathway activity was related to a favorable DFS and overall survival (OS) in postmenopausal women (p = 0.033 and p = 0.041, respectively), but not in premenopausal women. We divided the postmenopausal group into subgroups based on ER pathway activity quartiles. Survival analysis revealed that postmenopausal women in the lowest ER quartile had a shorter DFS and OS (log-rank p = 0.006 and p <
0.001, respectively). Furthermore, we were able to form subgroups of patients based on an inverse relation between ER and PI3K pathway activity. In conclusion, in postmenopausal patients with advanced stage HGSC, a poorer survival outcome was associated with low functional ER pathway activity.
Databáze: OpenAIRE
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