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醛酮还原酶1C3与子宫内膜癌患者更好的生存率相关。

AKR1C3 Is Associated with Better Survival of Patients with Endometrial Carcinomas.

作者信息

Hojnik Marko, Kenda Šuster Nataša, Smrkolj Špela, Frković Grazio Snježana, Verdenik Ivan, Rižner Tea Lanišnik

机构信息

Institute of Biochemistry, Faculty of Medicine, University of Ljubljana, 1000 Ljubljana, Slovenia.

Division of Gynecology, Department of Obstetrics and Gynecology, University Medical Centre Ljubljana, 1000 Ljubljana, Slovenia.

出版信息

J Clin Med. 2020 Dec 19;9(12):4105. doi: 10.3390/jcm9124105.

Abstract

The aldo-keto reductase (AKR) superfamily is gaining attention in cancer research. AKRs are involved in important biochemical processes and have crucial roles in carcinogenesis and chemoresistance. The enzyme AKR1C3 has many functions, which include production of prostaglandins, androgens and estrogens, and metabolism of different chemotherapeutics; AKR1C3 is thus implicated in the pathophysiology of different cancers. Endometrial and ovarian cancers represent the majority of gynecological malignancies in developed countries. Personalized treatments for these cancers depend on identification of prognostic and predictive biomarkers that allow stratification of patients. In this study, we evaluated the immunohistochemical (IHC) staining of AKR1C3 in 123 paraffin-embedded samples of endometrial cancer and 99 samples of ovarian cancer, and examined possible correlations between expression of AKR1C3 and other clinicopathological data. The IHC expression of AKR1C3 was higher in endometrial cancer compared to ovarian cancer. In endometrioid endometrial carcinoma, high AKR1C3 IHC expression correlated with better overall survival (hazard ratio, 0.19; 95% confidence interval, 0.06-0.65, = 0.008) and with disease-free survival (hazard ratio, 0.328; 95% confidence interval, 0.12-0.88, = 0.027). In patients with ovarian cancer, there was no correlation between AKR1C3 IHC expression and overall and disease-free survival or response to chemotherapy. These results demonstrate that AKR1C3 is a potential prognostic biomarker for endometrioid endometrial cancer.

摘要

醛糖酮还原酶(AKR)超家族在癌症研究中日益受到关注。AKR参与重要的生化过程,在致癌作用和化疗耐药性中发挥关键作用。酶AKR1C3具有多种功能,包括前列腺素、雄激素和雌激素的生成以及不同化疗药物的代谢;因此,AKR1C3与不同癌症的病理生理学相关。子宫内膜癌和卵巢癌是发达国家妇科恶性肿瘤的主要类型。这些癌症的个性化治疗取决于识别能够对患者进行分层的预后和预测生物标志物。在本研究中,我们评估了123例子宫内膜癌石蜡包埋样本和99例卵巢癌样本中AKR1C3的免疫组织化学(IHC)染色,并检查了AKR1C3表达与其他临床病理数据之间的可能相关性。与卵巢癌相比,子宫内膜癌中AKR1C3的IHC表达更高。在子宫内膜样子宫内膜癌中,高AKR1C3 IHC表达与更好的总生存期(风险比,0.19;95%置信区间,0.06 - 0.65,P = 0.008)和无病生存期(风险比,0.328;95%置信区间,0.12 - 0.88,P = 0.027)相关。在卵巢癌患者中,AKR1C3 IHC表达与总生存期、无病生存期或化疗反应之间无相关性。这些结果表明,AKR1C3是子宫内膜样子宫内膜癌的一种潜在预后生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/98cd/7766127/965af72a3939/jcm-09-04105-g001.jpg

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