Aberrant neuropepticle Y and macrophage inhibitory cytokine-1 expression are early events in prostate cancer development and are associated with poor prognosis
Aberrant neuropepticle Y and macrophage inhibitory cytokine-1 expression are early events in prostate cancer development and are associated with poor prognosis
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DOI：
10.1158/1055-9965.epi-05-0752
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发表时间：
2006-04-01
影响因子：
3.8
通讯作者：
Henshall, SM
中科院分区：
文献类型：
--
作者：
Rasiah, KK;Kench, JG;Henshall, SM
为阐明前列腺癌前病变中异常基因表达模式的研究已经确定了几个候选基因，它们有可能成为预防前列腺癌发生和发展的靶点，并作为早期疾病的生物标志物。在此，我们探讨了神经肽Y(NPY)和巨噬细胞抑制细胞因子-1(MIC-1)这两种蛋白作为前列腺癌侵袭前疾病生物标志物的重要性，并探讨其表达与局限性前列腺癌治疗后生化复发的关系。应用免疫组织化学方法检测243例前列腺癌根治术患者前列腺癌、良性、低度恶性前列腺上皮内瘤变(PIN)、高度恶性PIN(HGPIN)组织芯片中NPY和MIC-1蛋白的表达。NPY和MIC-1在HGPIN和前列腺癌中的表达比例均高于良性上皮(P<；0.0001)。NPY和MIC-1在低度恶性肾癌中的表达高于其他良性组织(均P<；0.0001)，与HGPIN中的表达相当。在调整了传统预后因素后，前列腺癌NPY免疫染色作为分类变量(P=0.0449-0.0103)和连续变量(P=0.0017)与复发独立相关。在调整了病理分期的预测因素后，低MIC-1免疫染色(20%类别)与病理分期有关(P=0.3894-0.0176)。这是第一项表明NPY和MIC-1表达改变与前列腺癌进展显著相关的研究，并表明这些分子可进一步发展为前列腺癌治疗中的生物标记物。
Studies to elucidate dysregulated gene expression patterns in premalignant prostate lesions have identified several candidate genes with the potential to be targeted to prevent the development and progression of prostate cancer and act as biomarkers of early disease. Herein, we explored the importance of two proteins, neuropeptide Y (NPY) and macrophage inhibitory cytokine-1 (MIC-1), as biomarkers of preinvasive prostate disease and investigated the relationship of expression to biochemical recurrence following treatment for localized prostate cancer. NPY and MIC-1 protein expression was determined by immunohistochemistry on tissue microarrays containing 1,626 cores of benign, low-grade prostatic intraepithelial neoplasia (PIN), highgrade PIN (HGPIN), and prostate cancer tissue from 243 radical prostatectomy patients. Both NPY and MIC-1 showed higher proportional immunostaining in HGPIN and prostate cancer compared with benign epithelium (P < 0.0001). NPY and MIC-1 immunostaining was higher in low-grade PIN compared with other benign tissues (both P < 0.0001) and was equivalent to immunostaining in HGPIN. NPY immunostaining of prostate cancer was independently associated with relapse, after adjusting for traditional prognostic factors, as a categorical variable in 20% intervals (P = 0.0449-0.0103) and as a continuous variable (P = 0.0017). Low MIC-1 immunostaining (20% categories) was associated with pathologic stage > 2C after adjusting for predictors of pathologic stage (P = 0.3894-0.0176). This is the first study to show that altered NPY and MIC-1 expression are significantly associated with prostate cancer progression and suggests that these molecules be developed further as biomarkers in the management of prostate disease.