JM-27 as a Potential Biomarker of Symptomatic BPH.

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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.