Clinical Significance of Wnt/β-Catenin Signalling and Androgen Receptor Expression in Prostate Cancer.

Clinical Significance of Wnt/β-Catenin Signalling and Androgen Receptor Expression in Prostate Cancer.
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DOI:
10.5534/wjmh.2013.31.1.36
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发表时间:
2013-04
期刊:
The world journal of men's health
影响因子:
--
通讯作者:
Kang DI
Kang DI
中科院分区:
其他
文献类型:
--
作者:
Jung SJ;Oh S;Lee GT;Chung J;Min K;Yoon J;Kim W;Ryu DS;Kim IY;Kang DI

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探讨Wnt/β-catenin通路、雄激素受体(AR)与前列腺癌临床病理因素的关系。本研究对132例接受前列腺切除术和前列腺针吸活检治疗的激素初治前列腺癌患者进行了研究。使用抗β-连环蛋白、基质金属蛋白酶-7(MMP-7)和AR的抗体进行免疫组织化学研究。对于体外研究,使用PC-3、LNCaP、22 Rv 1和DU 145细胞系。临床或病理分期:局限性癌36例(27.3%),局部晚期癌31例(23.5%),转移癌65例(49.2%)。我们检测到β-catenin、AR和MMP-7表达增加,Gleason分级高,疾病进展,血清前列腺特异性抗原(PSA)水平升高(p<0.01)。在斯皮尔曼等级相关中,发现胞浆β-catenin、MMP-7和AR的表达显著正相关。此外,β-catenin、MMP-7和AR的表达与提示预后不良的临床病理变量显著相关。49例原发性雄激素剥夺患者从激素治疗到PSA进展的反应持续时间较短,Kaplan-Meier曲线上MMP-7表达升高(p=0.0036)。这些数据表明,前列腺癌中活化的Wnt/β-连环蛋白途径和AR表达与转移和侵袭性相关。此外,MMP-7蛋白(Wnt/β-catenin途径的靶点)的表达与接受主要激素治疗的前列腺癌患者的PSA进展相关。
To investigate the relationships among the Wnt/β-catenin pathway, androgen receptor (AR), and clinicopathological factors in hormone-naïve prostate cancer. This study was conducted with132 cases of hormone-naïve prostate cancer treated by prostatectomy and prostate needle biopsy. An immunohistochemical study using antibodies against β-catenin, matrix metalloproteinase-7 (MMP-7), and the AR was performed. For the in vitro study, PC-3, LNCaP, 22Rv1, and DU145 cell lines were used. The clinical or pathological stage ware a localized cancer in 36 patients (27.3%), locally advanced cancer in 31 (23.5%), and metastatic cancer in 65 (49.2%). We detected increased β-catenin, AR, and MMP-7 expression with a high Gleason grade, disease progression, and increasing serum prostate-specific antigen (PSA) levels (p<0.01). In Spearman's rank correlations, the expression of cytoplasmic β-catenin, MMP-7, and the AR were found to be significantly positively correlated. In addition, the expression of β-catenin, MMP-7, and the AR were significantly correlated with clinicopathological variables indicative of a poor prognosis. Forty-nine patients with primary androgen deprivation had short response durations from hormone therapy to PSA progression with elevated MMP-7 expression on the Kaplan-Meier curve (p=0.0036). These data show that an activated Wnt/β-catenin pathway and AR expression in prostate cancer are correlated with metastasis and aggressiveness. In addition, the expression of MMP-7 protein, a target of the Wnt/β-catenin pathway, is associated with PSA progression in prostate cancer patients undergoing primary hormone therapy.