Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma

Background: Expression of the progesterone receptor (PR) has been reported to influence survival outcomes in patients with ovarian high-grade serous carcinoma (HGSC). In the present study, we attempted to investigate the association among PR and its isoforms’ expression, platinum sensitivity, and su...

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Autores principales:	Hao Lin, Kuo-Chung Lan, Yu-Che Ou, Chen-Hsuan Wu, Hong-Yo Kang, I-Chieh Chuang, Hung-Chun Fu
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	progesterone receptor-B platinum sensitivity ovarian high-grade serous carcinoma prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/dcec033c50f04af2aeecd035d750f459
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spelling	oai:doaj.org-article:dcec033c50f04af2aeecd035d750f4592021-11-11T15:35:57ZHighly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma10.3390/cancers132155782072-6694https://doaj.org/article/dcec033c50f04af2aeecd035d750f4592021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/21/5578https://doaj.org/toc/2072-6694Background: Expression of the progesterone receptor (PR) has been reported to influence survival outcomes in patients with ovarian high-grade serous carcinoma (HGSC). In the present study, we attempted to investigate the association among PR and its isoforms’ expression, platinum sensitivity, and survival in ovarian HGSC. Material and methods: This retrospective study reviewed ovarian HGSC patients who received surgery followed by adjuvant chemotherapy. We analyzed total PR and PR isoform-B (PR-B) expression by immunohistochemical staining and quantified using the H-score. Then, we compared platinum sensitivity and survival outcomes between those patients with weak and strong PR-B expression. Cisplatin viability assays were carried out in ovarian HGSC cell lines (OC-3-VGH and OVCAR-3) with different PR-B expression. Results: Among 90 patients, 49 and 41 patients were considered to have platinum-sensitive and platinum-resistant disease, respectively. Pearson’s correlation model showed that the H-score of total PR correlated positively with PR-B (<i>r</i> = 0.813). The PR-B H-score of tumors was significantly higher in the platinum-sensitive group (<i>p</i> = 0.004). Multivariate analysis revealed that the PR-B H-score and optimal debulking status were independent factors predicting platinum sensitivity. When compared with strong PR-B expression, patients with weak PR-B had significantly poorer progression-free (<i>p =</i> 0.021) and cancer-specific survival (<i>p</i> = 0.046). In a cell model, cisplatin-resistant OC-3-VGH cells expressed a lower level of PR-B than wild-type cells. Overexpression of PR-B or progesterone could increase cisplatin sensitivity in both OC-3-VGH and OVCAR-3 cells via the mechanism of promoting cisplatin-related apoptosis. Conclusions: When compared to weak PR-B, ovarian HGSC patients with a strong PR-B expression had a better chance of platinum sensitivity and survival, and this finding was compatible with our experimental results. Progesterone seemed to be a platinum sensitizer, but the value of adding progesterone in the treatment of ovarian HGSC should be further investigated.Hao LinKuo-Chung LanYu-Che OuChen-Hsuan WuHong-Yo KangI-Chieh ChuangHung-Chun FuMDPI AGarticleprogesterone receptor-Bplatinum sensitivityovarian high-grade serous carcinomaprognosisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5578, p 5578 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	progesterone receptor-B platinum sensitivity ovarian high-grade serous carcinoma prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	progesterone receptor-B platinum sensitivity ovarian high-grade serous carcinoma prognosis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Hao Lin Kuo-Chung Lan Yu-Che Ou Chen-Hsuan Wu Hong-Yo Kang I-Chieh Chuang Hung-Chun Fu Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma
description	Background: Expression of the progesterone receptor (PR) has been reported to influence survival outcomes in patients with ovarian high-grade serous carcinoma (HGSC). In the present study, we attempted to investigate the association among PR and its isoforms’ expression, platinum sensitivity, and survival in ovarian HGSC. Material and methods: This retrospective study reviewed ovarian HGSC patients who received surgery followed by adjuvant chemotherapy. We analyzed total PR and PR isoform-B (PR-B) expression by immunohistochemical staining and quantified using the H-score. Then, we compared platinum sensitivity and survival outcomes between those patients with weak and strong PR-B expression. Cisplatin viability assays were carried out in ovarian HGSC cell lines (OC-3-VGH and OVCAR-3) with different PR-B expression. Results: Among 90 patients, 49 and 41 patients were considered to have platinum-sensitive and platinum-resistant disease, respectively. Pearson’s correlation model showed that the H-score of total PR correlated positively with PR-B (<i>r</i> = 0.813). The PR-B H-score of tumors was significantly higher in the platinum-sensitive group (<i>p</i> = 0.004). Multivariate analysis revealed that the PR-B H-score and optimal debulking status were independent factors predicting platinum sensitivity. When compared with strong PR-B expression, patients with weak PR-B had significantly poorer progression-free (<i>p =</i> 0.021) and cancer-specific survival (<i>p</i> = 0.046). In a cell model, cisplatin-resistant OC-3-VGH cells expressed a lower level of PR-B than wild-type cells. Overexpression of PR-B or progesterone could increase cisplatin sensitivity in both OC-3-VGH and OVCAR-3 cells via the mechanism of promoting cisplatin-related apoptosis. Conclusions: When compared to weak PR-B, ovarian HGSC patients with a strong PR-B expression had a better chance of platinum sensitivity and survival, and this finding was compatible with our experimental results. Progesterone seemed to be a platinum sensitizer, but the value of adding progesterone in the treatment of ovarian HGSC should be further investigated.
format	article
author	Hao Lin Kuo-Chung Lan Yu-Che Ou Chen-Hsuan Wu Hong-Yo Kang I-Chieh Chuang Hung-Chun Fu
author_facet	Hao Lin Kuo-Chung Lan Yu-Che Ou Chen-Hsuan Wu Hong-Yo Kang I-Chieh Chuang Hung-Chun Fu
author_sort	Hao Lin
title	Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma
title_short	Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma
title_full	Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma
title_fullStr	Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma
title_full_unstemmed	Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma
title_sort	highly expressed progesterone receptor b isoform increases platinum sensitivity and survival of ovarian high-grade serous carcinoma
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/dcec033c50f04af2aeecd035d750f459
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Highly Expressed Progesterone Receptor B Isoform Increases Platinum Sensitivity and Survival of Ovarian High-Grade Serous Carcinoma

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