多梳蛋白 BMI-1 作为黏液性卵巢癌的潜在治疗靶点。

Polycomb Protein BMI-1 as a Potential Therapeutic Target in Mucinous Ovarian Cancer.

机构信息

Tumorbank Ovarian Cancer Network, Charité Universitätsmedizin Berlin, Corporate Μember of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany;

Department of Gynecology with Center of Oncological Surgery, European Competence Center for Ovarian Cancer, Charit Universittsmedizin Berlin, Corporate Member of Freie Universität Berlin, Humboldt-Universität zu Berlin, and Berlin Institute of Health, Berlin, Germany.

出版信息

Anticancer Res. 2022 Apr;42(4):1739-1747. doi: 10.21873/anticanres.15650.

DOI:10.21873/anticanres.15650

PMID:35346992

Abstract

BACKGROUND/AIM: Mucinous ovarian carcinoma (mOC) is a rare subtype with distinct clinical characteristics and biological behavior that differentiate them from other epithelial ovarian cancers. This study aimed to evaluate BMI-1 expression as a potential target for therapeutic approaches in advanced stage mOC.

MATERIALS AND METHODS

We performed gene set, as well as transcription factor enrichment analysis and immunohistochemistry assessing of the BMI-1 protein levels in tissue specimens of eighteen mucinous ovarian cancer patients. To validate the clinical relevance of the findings, we performed cell viability assays and western blot analysis utilizing high-grade serous (HGSC) and mOC cell lines.

RESULTS

BMI1 expression was not significantly associated with patient age, FIGO stage, lymph node status, and family history. With regard to progression-free survival, there was also no significant association (p=0.418). Cell viability was significant decreased in response to carboplatin in HGSC cells TYK-nu and OVHASO, and in mOC cell lines COV644 and EFO-27. Western blot analysis demonstrated various expression levels across all cell lines.

CONCLUSION

BMI-1 could be a useful potential therapeutic target in some ovarian cancer patients, including mOC patients.

摘要

背景/目的：黏液性卵巢癌（mOC）是一种罕见的亚型，具有独特的临床特征和生物学行为，与其他上皮性卵巢癌不同。本研究旨在评估 BMI-1 表达作为晚期 mOC 治疗方法的潜在靶点。

材料和方法

我们对 18 名黏液性卵巢癌患者的组织标本进行了基因集以及转录因子富集分析和免疫组织化学评估，以评估 BMI-1 蛋白水平。为了验证研究结果的临床相关性，我们利用高级别浆液性（HGSC）和 mOC 细胞系进行了细胞活力测定和 Western blot 分析。

结果

BMI1 表达与患者年龄、FIGO 分期、淋巴结状态和家族史均无显著相关性。就无进展生存期而言，也没有显著相关性（p=0.418）。在 HGSC 细胞系 TYK-nu 和 OVHASO 以及 mOC 细胞系 COV644 和 EFO-27 中，细胞活力在顺铂治疗后显著降低。Western blot 分析表明，所有细胞系的表达水平各不相同。