Abstract:
The treatment of ovarian cancer (OC) remains one of the greatest challenges in gynaecological oncology. The presence of classic steroid receptors in OC makes hormone therapy an attractive option; however, the response of OC to hormone therapy is modest. Here, we compared the expression patterns of progesterone (PGR), androgen (AR) and oestrogen alpha (ERα) receptors between serous OC cell lines and non-cancer ovarian cells. These data were analysed in relation to steroid receptor expression profiles from patient tumour samples and survival outcomes using a bioinformatics approach. The results showed that ERα, PGR and AR were co-expressed in OC cell lines, and patient samples from high-grade and low-grade OC co-expressed at least two steroid receptors. High AR expression was negatively correlated, whereas ERα and PGR expression was positively correlated with patient survival. AR showed the opposite expression pattern to that of ERα and PGR in type 1 (SKOV-3) and 2 (OVCAR-3) OC cell lines compared with non-cancer (HOSEpiC) ovarian cells, with AR downregulated in type 1 and upregulated in type 2 OC. A low AR/PGR ratio and a high ESR1/AR ratio were associated with favourable survival outcomes in OC compared with other receptor ratios. Although the results must be interpreted with caution because of the small number of primary tumour samples analysed, they nevertheless suggest that the evaluation of ERα, AR and PGR by immunohistochemistry should be performed in patient biological material to plan future clinical trials.
摘要:
卵巢癌(OC)的治疗仍然是妇科肿瘤学的最大挑战之一。OC中经典类固醇受体的存在使激素治疗成为一种有吸引力的选择;然而,OC对激素治疗的反应不大。这里,我们比较了孕酮(PGR)的表达模式,浆液性OC细胞系和非癌卵巢细胞之间的雄激素(AR)和雌激素α(ERα)受体。使用生物信息学方法分析了这些数据与来自患者肿瘤样品的类固醇受体表达谱和生存结果有关。结果表明,ERα,PGR和AR在OC细胞系中共表达,和来自高等级和低等级OC的患者样品共表达至少两种类固醇受体。AR高表达呈负相关,而ERα和PGR表达与患者生存率呈正相关。与非癌症(HOSEpiC)卵巢细胞相比,AR在1型(SKOV-3)和2型(OVCAR-3)OC细胞系中显示出与ERα和PGR相反的表达模式,AR在1型中下调,在2型OC中上调。与其他受体比率相比,低AR/PGR比率和高ESRl/AR比率与OC的有利生存结果相关。尽管由于分析的原发性肿瘤样本数量少,必须谨慎解释结果,然而,他们建议对ERα的评估,应在患者生物材料中通过免疫组织化学进行AR和PGR,以计划未来的临床试验。