Clinical Significance of Polymorphism and Expression of Chromogranin A and Endothelin-1 in Prostate Cancer

Clinical Significance of Polymorphism and Expression of Chromogranin A and Endothelin-1 in Prostate Cancer
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DOI:
10.1016/j.juro.2010.04.063
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发表时间:
2010-09-01
期刊:
影响因子:
6.6
通讯作者:
Habuchi, Tomonori
Habuchi, Tomonori
中科院分区:
医学1区
文献类型:
--
作者:
Ma, Zhiyong;Tsuchiya, Norihiko;Habuchi, Tomonori

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目的:材料与方法:采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术,对435例前列腺癌患者和316例年龄匹配的男性对照者的CHGA基因多态性进行分析。采用免疫组织化学方法对114例前列腺癌患者行根治性耻骨后前列腺切除术的前列腺标本和27例膀胱癌患者行根治性膀胱切除术的前列腺标本中嗜铬粒蛋白A和内皮素-1的表达进行了评价。对于CHGA Glu 264 Asp多态性,GG基因型男性患前列腺癌的风险是CC基因型男性的2.05倍(p = 0.014)。在前列腺癌患者中,嗜铬粒蛋白A免疫组化分级越高,分期越高,Gleason评分越高(分别为p = 0.011和0.044)。多因素分析显示嗜铬粒蛋白A免疫组化分级是预测根治性乳腺癌切除术后生化失败的独立变量(p = 0.023)。在前列腺癌中观察到更高的内皮素-1表达(p = 0.011),尤其是具有更高Gleason评分的那些(p = 0.042)。结论:嗜铬粒蛋白A和内皮素-1基因多态性及表达在前列腺癌中具有临床意义。嗜铬粒蛋白A表达是局限性前列腺癌患者前列腺切除术后生化失败的独立预测因子。
Purpose: We investigated the clinical significance of chromogranin A and endothelin-1 polymorphism and expression in prostate cancer.Materials and Methods: We analyzed 2 CHGA polymorphisms by polymerase chain reaction-restriction fragment length polymorphism in DNA samples of 435 patients with prostate cancer and 316 age matched male controls. Chromogranin A and endothelin-1 expression was evaluated by immunohistochemistry in prostate specimens of 114 men with prostate cancer who underwent radical retropubic prostatectomy and in 27 with bladder cancer who underwent radical cystectomy and served as controls.Results: For the CHGA Glu264Asp polymorphism men with the GG genotype were at 2.05 times higher risk for prostate cancer than men with the CC genotype (p = 0.014). In men with prostate cancer higher chromogranin A immunohistochemistry grade was associated with higher stage and higher Gleason score (p = 0.011 and 0.044, respectively). Multivariate analysis showed that chromogranin A immunohistochemistry grade was an independent variable for predicting biochemical failure after radical prostatectomy (p = 0.023). Higher endothelin-1 expression was observed in prostate cancers (p = 0.011), especially those with a higher Gleason score (p = 0.042). There was no significant relationship between chromogranin A polymorphisms, and chromogranin A and endothelin-1 expression.Conclusions: Polymorphism and expression of chromogranin A and endothelin-1 have clinical significance in prostate cancer. Chromogranin A expression was an independent predictor of biochemical failure after prostatectomy in patients with localized prostate cancer.