Department of Gynecology and Obstetrics, University Medical Center Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
Department of Pathology, University Medical Center Regensburg, Franz-Josef Strauß Allee11, 93053, Regensburg, Germany.
J Cancer Res Clin Oncol. 2021 Sep;147(9):2555-2567. doi: 10.1007/s00432-021-03673-9. Epub 2021 Jun 5.
This study further approaches the role of estrogen-related receptors (ERRs) in ovarian cancer. Protein expression of ERRα, ERRβ and ERRγ in ovarian cancer was assessed and was correlated with ovarian cancer markers, steroid hormone receptors and cancer-associated genes. Additionally, we examined to what extent expression of ERRs affects survival of ovarian cancer patients.
For this purpose, we established a tissue microarray from 208 ovarian cancer patients and performed immunohistochemical analyses of the mentioned proteins.
ERRα and ERRγ protein could be detected at different levels in more than 90% of all ovarian cancer tissues, whereas expression of ERRβ was observed in 82.2% of the cases. ERRα was found to positively correlate with ovarian cancer marker CEA (p < 0.005) and ERRγ correlated with ERα (p < 0.001). Univariate survival analyses revealed that ERRα expression did not affect overall (OS) or progression-free survival (PFS) of ovarian cancer patients. In contrast, higher expression of ERRβ in serous ovarian cancers was found to lead to a significantly decreased OS (p < 0.05). The strongest impact on survival was exhibited by ERRγ. Lower expression of this receptor in women with serous ovarian cancers indicated significantly increased OS compared to those with higher levels of ERRγ (p < 0.05). Multivariate survival analyses revealed ERRγ as an independent prognostic marker regarding OS of patients with serous ovarian cancer.
Our data demonstrating that ERR proteins are frequently expressed in ovarian cancer and high levels of ERRβ and ERRγ significantly decreased OS of serous ovarian cancer patients suggest that these proteins might be interesting therapy targets in this cancer entity.
本研究进一步探讨了雌激素相关受体（ERRs）在卵巢癌中的作用。评估了卵巢癌中 ERRα、ERRβ 和 ERRγ 的蛋白表达，并将其与卵巢癌标志物、类固醇激素受体和癌相关基因相关联。此外，我们还研究了 ERRs 的表达在多大程度上影响卵巢癌患者的生存。
为此，我们从 208 例卵巢癌患者中建立了一个组织微阵列，并对上述蛋白进行了免疫组织化学分析。
ERRα 和 ERRγ 蛋白在超过 90%的所有卵巢癌组织中可以检测到不同水平，而 ERRβ 的表达在 82.2%的病例中观察到。ERRα 的表达与卵巢癌标志物 CEA 呈正相关（p<0.005），ERRγ 与 ERα 呈正相关（p<0.001）。单变量生存分析显示，ERRα 的表达并不影响卵巢癌患者的总生存期（OS）或无进展生存期（PFS）。相反，在浆液性卵巢癌中，ERRβ 的高表达与 OS 显著降低相关（p<0.05）。ERRγ 对生存的影响最大。在浆液性卵巢癌患者中，该受体的低表达表明与高表达 ERRγ 的患者相比，OS 显著增加（p<0.05）。多变量生存分析显示，ERRγ 是浆液性卵巢癌患者 OS 的独立预后标志物。
我们的数据表明，ERR 蛋白在卵巢癌中经常表达，ERRβ 和 ERRγ 的高水平显著降低了浆液性卵巢癌患者的 OS，这表明这些蛋白可能是该癌症实体中有趣的治疗靶点。
