Overexpression of vasoactive intestinal peptide receptors and cyclooxygenase-2 in human prostate cancer. Analysis of potential prognostic relevance
Overexpression of vasoactive intestinal peptide receptors and cyclooxygenase-2 in human prostate cancer. Analysis of potential prognostic relevance
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DOI：
10.14670/hh-27.1093
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发表时间：
2012-08-01
影响因子：
2
通讯作者：
Sanchez-Chapado, Manuel
中科院分区：
文献类型：
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作者：
Fernandez-Martinez, Ana B.;Carmena, Maria J.;Sanchez-Chapado, Manuel
血管活性肠肽（VIP）是前列腺癌细胞系中环氧合酶-2（考克斯-2）表达的有效诱导剂。关于考克斯-2在该疾病进展中的作用存在相互矛盾的数据。在此，我们检测了前列腺癌标本中VIP受体（VPAC（1）和VPAC（2））和考克斯-2的表达。统计分析蛋白水平与各种临床病理因素及患者预后的相关性。为了这些目的，使用了来自63名前列腺癌患者和9名对照样本的福尔马林固定、石蜡包埋的前列腺组织标本。采用定量逆转录聚合酶链反应（RT-PCR）检测VPAC（1）和VPAC（2）受体及考克斯-2（COX-2）mRNA水平的表达。通过免疫组化研究相应蛋白水平的表达，评分为阴性、弱、中度或强，并通过多变量分析与不同临床病理因素相关。88%的前列腺癌组织中VPAC（1）-受体mRNA过表达，72%的前列腺癌组织中VPAC（2）-受体mRNA过表达，77%的前列腺癌组织中考克斯-2 mRNA过表达。52%的患者同时出现三种基因的过度表达。在蛋白质水平上观察到类似的过表达模式。VPAC（1）和VPAC（2）受体蛋白水平之间的相关性具有统计学意义。VPAC受体和考克斯-2蛋白表达水平与患者年龄、PSA水平、肿瘤分期、Gleason评分及生存期无明显相关性。VPAC（1）和VPAC（2）受体以及考克斯-2在癌组织中的过表达使它们具有作为前列腺癌诊断靶点的潜在作用，但结果不支持作为该疾病临床预后的生物标志物的明确价值。
Vasoactive intestinal peptide (VIP) is a potent inductor of cyclooxygenase-2 (COX-2) expression in human prostate cancer cell lines. There are conflicting data regarding the role of COX-2 in the progression of this disease. Here we examined the expression of VIP receptors (VPAC(1) and VPAC(2)) and COX-2 in prostate cancer specimens. Correlations among protein levels and various clinicopathological factors and prognosis of patients were statistically analyzed. For these purposes, formaldehyde-fixed, paraffin-embedded prostate tissue specimens from 63 patients with prostate cancer and 9 control samples were used. The expression of VPAC(1) and VPAC(2) receptors and COX-2 was analyzed at mRNA levels by quantitative reverse transcriptase-PCR. The corresponding expression at protein level was studied by immunohistochemistry, scored as negative, weak, moderate, or strong, and correlated with different clinicopathological factors by means of multivariate analysis. 88% of prostate cancer tissues overexpressed VPAC(1)-receptor at mRNA level, 72% VPAC(2)-receptor and 77% COX-2. Simultaneous overexpression of the three genes was seen in 52% of patients. Similar overexpression patterns were observed at protein level. The correlation between VPAC(1) and VPAC(2) receptor protein levels was statistically significant. However, no significant correlations existed among protein levels of VPAC receptors and COX-2 with patient age, prostate-specific antigen (PSA) levels, tumor stage, Gleason score and survival time. The overexpression of VPAC(1) and VPAC(2) receptors and COX-2 in cancer tissue gives them a potential role as targets for diagnosis of prostate cancer but results do not support a clear value as biomarkers for the clinical prognosis of this disease.