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

Abstract

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.

Functional estrogen receptor signal transduction pathway activity and antihormonal therapy response in low‐grade ovarian carcinoma

“…The STP activity of seven STPs was determined using an STP assay (version 1.15.2; Philips) 22–25 . The results are reported as quantitative measurements on a scale from 0 to 100, representing the functional activity of each pathway.…”

“…The STP activity of seven STPs was determined using an STP assay (version 1.15.2; Philips). [22][23][24][25] The results are reported as quantitative measurements on a scale from 0 to 100, representing the functional activity of each pathway. On this scale, 0 corresponds to the lowest odds, and 100 corresponds to the highest odds in favor of active pathway activity.…”

Phenotype-Guided Targeted Therapy Based on Functional Signal Transduction Pathway Activity in Recurrent Ovarian Cancer Patients: The Stapover Study Protocol

“…3. This format contains the STP activity distributions measured in previous cohorts of normal FTE (blue curve), HGSC samples (red curve) and low-grade serous ovarian carcinoma (LGSC) samples (purple curve) [28,29,43]. For each measured STP, data is displayed in a single graph.…”

“…Our research group investigated STP activity in several subtypes of ovarian cancer to identify which STPs could be potential targets for personalized medicine [27,28]. Furthermore, we determined STP activity in morphologically normal Fallopian tube epithelium (FTE) of healthy women, the considered tissue of origin of most high-grade serous carcinoma (HGSC), to establish normal STP activity as a reference.…”

Prognostic Value of Lymph Node Parameters in Elderly Patients With Stage III Serous Ovarian Cancer Based on Competing Risk Model

“…A s the eighth most prevalent disease and the fifth greatest cause of cancer-related death among women globally, ovarian cancer is a serious threat to public health. 1,2 Ovarian cancer has a usually dismal prognosis, with a 5-year survival rate of roughly 30%. 3,4 Unfortunately, there is no effective early diagnosis method due to the concealed early clinical symptoms.…”