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孕激素受体表达如何影响卵巢透明细胞癌对铂类药物的敏感性:来自临床和实验视角的见解。

How Progesterone Receptor Expression Impacts Platinum Sensitivity in Ovarian Clear Cell Carcinoma: Insights from Clinical and Experimental Perspectives.

机构信息

Department of Obstetrics and Gynecology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 833, Taiwan.

Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan.

出版信息

Int J Mol Sci. 2024 Jul 20;25(14):7942. doi: 10.3390/ijms25147942.

Abstract

Ovarian clear cell carcinoma (OCCC) is often considered a relatively platinum-resistant malignancy. The aim of this study was to explore the influence of progesterone receptor (PR) expression levels on platinum sensitivity and survival outcomes in people with OCCC. A retrospective analysis was conducted with 80 people with OCCC who underwent surgery followed by adjuvant chemotherapy. PR expression was assessed via immunohistochemical (IHC) staining and quantified using the H score. The platinum sensitivity and survival outcomes of patients with weak and strong PR expression were compared. Additionally, cisplatin viability and migration experiments were conducted with OCCC cell lines (ES-2 and TOV-21G) with varying PR isoform expressions. Among the 80 patients, 62 were classified as having platinum-sensitive disease, while 18 had platinum-resistant disease. The mean total PR H- score of platinum-sensitive tumors was significantly higher than that of platinum-resistant tumors ( = 0.002). Although no significant differences in progression-free and overall survival were observed between patients with high and low PR expression, those with high PR expression tended to have longer survival. While PR protein was only weakly detectable in ES-2 and TOV-21G cells, a transfection of the PR-A or PR-B gene resulted in a strong expression of PR-A or PR-B, which led to significantly reduced proliferation and migration in ES-2 and TOV-21G cells. Furthermore, overexpression of PR-A or PR-B enhanced cisplatin cytotoxicity in these cell lines. In conclusion, strong PR expression was associated with improved platinum sensitivity and survival outcomes, consistent with our experimental findings. The potential of PR as a tumor sensitizer to cisplatin in OCCC warrants further investigation.

摘要

卵巢透明细胞癌(OCCC)通常被认为是一种相对铂类耐药的恶性肿瘤。本研究旨在探讨孕激素受体(PR)表达水平对 OCCC 患者铂类敏感性和生存结局的影响。对 80 例接受手术和辅助化疗的 OCCC 患者进行回顾性分析。采用免疫组织化学(IHC)染色法检测 PR 表达,并采用 H 评分进行定量。比较 PR 弱表达和强表达患者的铂类敏感性和生存结局。此外,还利用 PR 异构体表达不同的 OCCC 细胞系(ES-2 和 TOV-21G)进行顺铂活力和迁移实验。在 80 例患者中,62 例被归类为铂类敏感疾病,18 例为铂类耐药疾病。铂类敏感肿瘤的总 PR H 评分明显高于铂类耐药肿瘤( = 0.002)。虽然高 PR 表达和低 PR 表达的患者在无进展生存期和总生存期方面没有显著差异,但高 PR 表达的患者倾向于有更长的生存时间。虽然 PR 蛋白在 ES-2 和 TOV-21G 细胞中仅微弱可检测到,但 PR-A 或 PR-B 基因的转染导致 PR-A 或 PR-B 的强表达,这导致 ES-2 和 TOV-21G 细胞的增殖和迁移明显减少。此外,PR-A 或 PR-B 的过表达增强了这些细胞系中顺铂的细胞毒性。总之,强 PR 表达与改善铂类敏感性和生存结局相关,与我们的实验结果一致。PR 作为 OCCC 中顺铂增敏剂的潜力值得进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6b1a/11276830/575506ed2b62/ijms-25-07942-g001.jpg

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