Abstract
Hormone receptor expression patterns often correlate with infiltration of specific lymphocytes in tumors. Specifically, the presence of specific tumor-infiltrating lymphocytes (TILs) with particular hormone receptor expression is reportedly associated with breast cancer, however, this has not been revealed in epithelial ovarian cancer (EOC). Therefore, we investigated the association between hormone receptor expression and TILs in EOC. Here we found that ERα, AR, and GR expression increased in EOC, while PR was significantly reduced and ERβ expression showed a reduced trend compared to normal epithelium. Cluster analysis indicated poor disease-free survival (DFS) in AR+/GR+/PR+ subgroup (triple dominant group); while the Cox proportional-hazards model high-lighted the triple dominant group as an independent prognostic factor for DFS. In addition, significant upregulation of FoxP3+ TILs, PD-1, and PD-L1 was observed in the triple dominant group compared to other groups. NanoString analyses further suggested that tumor necrosis factor (TNF) and/or NF-κB signaling pathways were activated with significant upregulation of RELA, MAP3K5, TNFAIP3, BCL2L1, RIPK1, TRAF2, PARP1, and AKT1 in the triple dominant EOC group. The triple dominant subgroup correlates with poor prognosis in EOC. Moreover, the TNF and/or NF-κB signaling pathways may be responsible for hormone-mediated inhibition of the immune microenvironment.
| Original language | English |
|---|---|
| Article number | 5714 |
| Journal | International journal of molecular sciences |
| Volume | 22 |
| Issue number | 11 |
| DOIs | |
| Publication status | Published - 2021 Jun 1 |
Bibliographical note
Funding Information:Funding: This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Korean government (MSIT) (NRF-2017M3A9B8069610).
Funding Information:
A total of 212 EOC, 57 borderline ovarian tumor, 153 benign epithelial ovarian tumors and 79 nonadjacent normal epithelial tissue samples were obtained from patients who underwent primary surgery at the Gangnam Severance Hospital between 2004 and 2012, and some of the samples were obtained from the Korea Gynecologic Cancer Bank as part of the Bio and Medical Technology Development Program of the Ministry of the National Research Foundation (NRF), funded by the Korean government (MIST) (NRF-2017M3A9B8069610). The International Federation of Gynecology and Obstetrics (FIGO) classification was used for tumor staging, and clinical information, including surgical procedure, survival time, survival status, and age, were collected by reviewing the medical records of the patients. The patients’ response to therapy was assessed by using computed tomography with Response Evaluation Criteria in Solid Tumors (RECIST; version 1.1). Tumor grade and cell type were evaluated by reviewing pathological reports, and all tumor samples were histologically examined by two gynecologic pathologists. All biological samples were collected after obtaining informed consent from participants, following the guidelines of the institutional review board (IRB) of the Gangnam Severance Hospital (IRB No. 3-2018-0122).
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.
All Science Journal Classification (ASJC) codes
- Catalysis
- Molecular Biology
- Spectroscopy
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
