JM-27 as a Potential Biomarker of Symptomatic BPH.

良性前列腺增生症(BPH)/下尿路症状(LUTS) 影响老年男性的生活质量。尽管良性前列腺增生症已经被公认为 有症状或无症状的疾病，这两种形式被认为在分子上是无法区分的 水平。为了阐明BPH背后的分子差异，来自前列腺的基因表达谱 用基因芯片分析过渡区。这些结果确定了几个似乎与 鉴别有严重症状和无症状的良性前列腺增生症。这 应用主要集中在其中一个基因上，即Ji^-27。JM-27(也称为PAGE4/GAGEC1)是 男性前列腺特异表达，在有症状但无症状的良性前列腺增生症中表达。 Ji/L-27在前列腺癌患者的BPH中也有表达，而且似乎是 仅在间质中优先表达。我们推测JM-27是一种前列腺癌间质细胞调节因子。 生长及其过度表达与症状性BPH有关。这一假设将通过以下方式得到解决 完成以下具体目标：1)全面分析JM-27蛋白的表达 正常成人前列腺、胎儿前列腺癌、前列腺癌以及有症状和无症状的前列腺增生症 应用免疫组织化学和免疫印迹技术的组织芯片，2)进一步评估 血清JM-27表达在鉴别症状性和非症状性BPH中的应用 已经开发出，并且3)使用这种ELISA法来分析来自参与的个人的全部样本 在NIDDK MTOPS研究中，并确定基于血清的JM-27识别 他们的疾病以及那些对治疗方式有反应的人的进展。这些数据可能 为早期识别患有BPH/LUTS的个体提供新的方法，导致 严重的症状提供了治疗干预的机会，并表现出 分子水平，那些对当前治疗有效或无效的药物。

Benign Prostatic Hyperplasia (BPH)/lower urinary tract symptoms (LUTS) is a disease that significantly affects the quality of life in aging men. Though BPH has been well recognized to present itself as symptomatic or asymptomatic disease, the two forms were thought to be indistinguishable at the molecular level. To elucidate the molecular differences underlying BPH, gene expression profiles from the prostate transition zone were analyzed using microarrays. These results identified several genes that appear to differentiate BPH from individuals with severe symptoms from those with asymptomatic BPH. This application focuses on one of these genes namely, JI^-27. JM-27 (also known as PAGE4/GAGEC1) is remarl<ably specific to the prostate in males and is expressed in symptomatic but not asymptomatic BPH. JI\/l-27 is also expressed in BPH from individuals with prostate cancer and furthermore, appears to be preferentially expressed only in the stroma. We hypothesize that JM-27 is a stromal cell regulator of prostatic growth and its overexpression is associated with symptomatic BPH. This hypothesis will be addressed by accomplishing the following specific aims: 1) to comprehensively analyze the expression of JM-27 protein in normal adult prostate, fetal prostate, prostate cancer as well as in symptomatic and asymptomatic BPH tissue microarrays using immunohistochemistry and immunoblotting, 2)to further evaluate the ability of serum JM-27 expression to differentiate symptomatic and asymptomatic BPH using the ELISA protocol we have developed, and 3) using this ELISA, to analyze the entire To samples from individuals that participate in the NIDDK MTOPS study and to determine the ability of serum-based JM-27 to identify individuals that progress with their disease as well as those that respond to the therapeutic modalities. These data could provide novel approaches for the early identification of individuals with the form of BPH/LUTS that results in severe symptoms providing for an opportunity for therapeutic intervention as well as to characterize, at the molecular level, those that respond or fail to respond to current treatments.