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分析在肌层浸润性膀胱癌中性激素受体 mRNA 表达的预后相关性。

Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder.

机构信息

Department of Urology, University Medical Centre Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.

Department of Urology and Pediatric Urology, Friedrich-Alexander University (FAU) Erlangen-Nürnberg, Erlangen, Germany.

出版信息

Virchows Arch. 2019 Feb;474(2):209-217. doi: 10.1007/s00428-018-2496-9. Epub 2018 Nov 27.


DOI:10.1007/s00428-018-2496-9
PMID:30483954
Abstract

Muscle-invasive urothelial carcinoma of the urinary bladder (UCB) often recurs following radical cystectomy (RC). An altered expression of sex-steroid hormone receptors has been associated with oncological outcomes of UCB and may represent therapeutic targets. Here the expression of different hormone receptors was measured on mRNA levels in patients treated by RC and associated with outcomes. Androgen receptor (AR), estrogen receptor 1 (ESR1), and progesterone receptor (PGR) mRNA expression was assessed by quantitative reverse transcription polymerase chain reaction (RT-qPCR) in RC samples of 87 patients with a median age of 66 (39-88) years. Univariate and multivariate analyses were performed to test associations with pathological and clinical characteristics as well as recurrence-free (RFS) and disease-specific survival (DSS). AR mRNA expression was lower in comparison with ESR1 and PGR expression (p < 0.0001). In univariate analysis, high expression levels of AR were associated with reduced RFS (HR 2.8, p = 0.015) and DSS (HR 2.8, p = 0.010). High AR mRNA expression and a positive lymph node status were independent predictors for reduced RFS (HR 2.5, p = 0.0049) and DSS (HR 3.4, p = 0.009). In patients with low AR mRNA expression, an increased ESR1 and PGR mRNA expression were associated with reduced RFS and DSS. High expression levels of AR are significantly associated with adverse outcome in patients with muscle-invasive UCB following RC. ESR1 and PGR expression status can further stratify patients with low AR expression into subgroups with significantly reduced RFS and DSS. Therapeutic targeting of AR may influence outcomes in patients with UCB.

摘要

肌层浸润性膀胱癌(UCB)患者在接受根治性膀胱切除术(RC)后常复发。性激素受体表达的改变与 UCB 的肿瘤学结果相关,可能代表治疗靶点。在此,研究人员通过定量逆转录聚合酶链反应(RT-qPCR)在 87 例接受 RC 治疗的患者的 RC 样本中测量了不同激素受体的 mRNA 水平,并将其与结局相关联。雄激素受体(AR)、雌激素受体 1(ESR1)和孕激素受体(PGR)mRNA 表达通过 RT-qPCR 进行评估,研究对象为 87 例患者,年龄中位数为 66 岁(39-88 岁)。进行单变量和多变量分析以检验与病理和临床特征以及无复发生存(RFS)和疾病特异性生存(DSS)的相关性。AR mRNA 表达水平低于 ESR1 和 PGR 表达水平(p<0.0001)。在单变量分析中,高 AR 表达水平与 RFS(HR 2.8,p=0.015)和 DSS(HR 2.8,p=0.010)降低相关。高 AR mRNA 表达和阳性淋巴结状态是 RFS(HR 2.5,p=0.0049)和 DSS(HR 3.4,p=0.009)降低的独立预测因素。在 AR mRNA 表达低的患者中,ESR1 和 PGR mRNA 表达增加与 RFS 和 DSS 降低相关。在接受 RC 治疗的肌层浸润性 UCB 患者中,AR 高表达与不良结局显著相关。ESR1 和 PGR 表达状态可进一步将 AR 低表达患者分为 RFS 和 DSS 显著降低的亚组。AR 的治疗靶向可能会影响 UCB 患者的结局。

相似文献

[1]
Analysis of the prognostic relevance of sex-steroid hormonal receptor mRNA expression in muscle-invasive urothelial carcinoma of the urinary bladder.

Virchows Arch. 2018-11-27

[2]
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BMC Cancer. 2019-4-8

[3]
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[4]
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[5]
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Urol Oncol. 2018-12

[6]
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[7]
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Pathol Oncol Res. 2018-6-3

[8]
Impact of smoking and smoking cessation on outcomes in bladder cancer patients treated with radical cystectomy.

Eur Urol. 2012-11-27

[9]
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BJU Int. 2012-1-5

[10]
Long Non-Coding RNA Cancer Susceptibility Candidate 2a (CASC2a) Is a Marker of Early Recurrence After Radical Cystectomy in Patients with Urothelial Carcinoma of the Bladder.

Med Sci Monit. 2018-1-23

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[2]
Identification of Prognostic Biomarkers for Bladder Cancer Based on DNA Methylation Profile.

Front Cell Dev Biol. 2022-1-31

[3]
The prognostic role of steroid hormone receptor signaling pathways in urothelial carcinoma.

Transl Cancer Res. 2020-10

[4]
KRT20, KRT5, ESR1 and ERBB2 Expression Can Predict Pathologic Outcome in Patients Undergoing Neoadjuvant Chemotherapy and Radical Cystectomy for Muscle-Invasive Bladder Cancer.

J Pers Med. 2021-5-26

[5]
Neuropilin-2 and Its Transcript Variants Correlate with Clinical Outcome in Bladder Cancer.

Genes (Basel). 2021-4-9

[6]
The Role of Estrogen Receptors in Urothelial Cancer.

Front Endocrinol (Lausanne). 2021

[7]
Reproductive and hormonal factors and bladder cancer risk: a prospective study and meta-analysis.

Aging (Albany NY). 2020-7-6

本文引用的文献

[1]
Tumor biomarker conversion between primary and metastatic breast cancer: mRNA assessment and its concordance with immunohistochemistry.

Oncotarget. 2017-5-19

[2]
FOXM1 predicts overall and disease specific survival in muscle-invasive urothelial carcinoma and presents a differential expression between bladder cancer subtypes.

Oncotarget. 2017-7-18

[3]
High Androgen Receptor mRNA Expression Is Independently Associated with Prolonged Cancer-Specific and Recurrence-Free Survival in Stage T1 Bladder Cancer.

Transl Oncol. 2017-6

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AR-Signaling in Human Malignancies: Prostate Cancer and Beyond.

Cancers (Basel). 2017-1-11

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In stage pT1 non-muscle-invasive bladder cancer (NMIBC), high KRT20 and low KRT5 mRNA expression identify the luminal subtype and predict recurrence and survival.

Virchows Arch. 2017-3

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Androgen receptor activation: a prospective therapeutic target for bladder cancer?

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ERBB2 Expression as Potential Risk-Stratification for Early Cystectomy in Patients with pT1 Bladder Cancer and Concomitant Carcinoma in situ.

Urol Int. 2017

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Closing the Gender Gap: Can We Improve Bladder Cancer Survival in Women? - A Systematic Review of Diagnosis, Treatment and Outcomes.

Urol Int. 2016

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J Urol. 2016-8-6

[10]
Technical validation of an RT-qPCR in vitro diagnostic test system for the determination of breast cancer molecular subtypes by quantification of ERBB2, ESR1, PGR and MKI67 mRNA levels from formalin-fixed paraffin-embedded breast tumor specimens.

BMC Cancer. 2016-7-7

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