Clinical significance of steroid and xenobiotic receptor and its targeted gene CYP3A4 in human prostate cancer
Clinical significance of steroid and xenobiotic receptor and its targeted gene CYP3A4 in human prostate cancer
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DOI：
10.1111/j.1349-7006.2011.02143.x
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发表时间：
2012-02-01
期刊：
影响因子：
5.7
通讯作者：
Inoue, Satoshi
中科院分区：
文献类型：
--
作者：
Fujimura, Tetsuya;Takahashi, Satoru;Inoue, Satoshi
类固醇和异源受体(SXR)调节细胞色素P450(CYP)酶，而细胞色素P450是肝脏和前列腺中睾酮的关键失活因子。在本研究中，我们研究了SXR在人前列腺组织中的表达。我们用抗SXR抗体检测了良性(n=78)和癌(n=106)前列腺癌组织中SXR免疫反应。染色后的切片观察免疫反应细胞的比例和染色强度。总免疫反应性(IR)评分(范围：08)为比例和强度分数之和。分析患者的临床病理特征、SXR状态和细胞色素P3A4免疫反应的关系。Western印迹分析证实了抗SXR抗体在293T细胞中的特异性。91%(71/78)的良性病灶和47%(50/106)的癌性病变呈核SXR染色阳性(IR积分=2)。癌性病变的免疫反应评分显著低于良性病变(P<；0.0001)。临床病理分析显示，高SXR IR评分(=4)患者的肿瘤特异性生存率显著增加(P=0.046)。目前和以往研究的综合数据显示，在多因素回归分析中，SXR和CYP3A4的高IR分数与显著更好的癌症特异性生存率相关(危险比：2.15，95%可信区间：1.253.55，P=0.007)。我们发现SXR在人前列腺组织中的表达存在差异。SXR和CYP3A4的高表达是前列腺癌预后良好的一个强有力的预后指标，并可能成为治疗的靶点。(《癌症科学》2012年版，第103期：176180页)
The steroid and xenobiotic receptor (SXR) regulates cytochrome P450 (CYP) enzymes, which are key inactivators of testosterone in the liver and prostate. In the present study, we investigated SXR expression in human prostate tissues. We determined SXR immunoreactivity using an anti-SXR antibody in benign (n = 78) and cancerous (n = 106) tissues obtained by radical prostatectomy. Stained slides were evaluated for the proportion and staining intensity of immunoreactive cells. Total immunoreactivity (IR) scores (range: 08) were calculated as the sum of the proportion and intensity scores. Associations between the clinicopathological features of the patients, SXR status, and CYP3A4 immunoreactivity were analyzed. Western blot analyses validated the specificity of the anti-SXR antibody in 293T cells transfected with pcDNAFLAGSXR. Positive (IR score: = 2) nuclear SXR staining was observed in 91% (71/78) of benign foci and 47% (50/106) of cancerous lesions. Immunoreactivity scores were significantly lower in the cancerous lesions than in the benign foci (P < 0.0001). Clinicopathological analyses showed that cancer-specific survival in patients with high SXR IR scores (=4) was significantly increased (P = 0.046). Combined data of present and previous studies showed that high IR scores for both the SXR and CYP3A4 correlated with significantly better cancer-specific survival rates in multivariate regression analyses (hazard ratio: 2.15, 95% confidence interval: 1.253.55, P = 0.007). We showed differential SXR expression in human prostate tissues. The high expression of the SXR and CYP3A4 is a strong prognostic indicator of favorable outcomes in prostate cancer, and could be a therapeutic target. (Cancer Sci 2012; 103: 176180)