Human Kallikrein 4 (hK4): A New Prostatic Biomarker?

描述（由申请人提供）：前列腺癌是一个主要的健康问题。不幸的是，我们还没有预防前列腺癌的有效方法。我们现在针对前列腺癌的最佳策略是早期诊断，然后进行明确的治疗。这种方法显著降低了前列腺癌的死亡率。前列腺癌的早期诊断最广泛使用的策略包括测量血清中的前列腺特异性抗原。这种方法确定了男性在高风险，随后，活检，以确认诊断。不幸的是，该测试不是很强大，大约5名患者必须进行活检才能检测出1例前列腺癌。显然，需要开发更多的用于诊断前列腺癌的生物标志物。 我们最近发现了一种新的基因，该基因与PSA属于同一家族，并且具有与PSA相似的其他特征，即该基因编码分泌型蛋白酶，该基因受雄激素调节，在前列腺中高度表达，并且该蛋白质被分泌到循环中。我们推测，在前列腺癌中编码的蛋白质人激肽释放酶4的水平也可能升高，并且除了PSA和其他生物标志物之外，hK4的测量可能显着提高我们特异性诊断早期前列腺癌的能力。在这项资助申请中，我们建议开发必要的技术来测量血清中的人激肽释放酶4，并进行探索性临床研究，以调查这种生物标志物的浓度是否确实在前列腺癌中增加，以及它与其他生物标志物的组合是否可以提高诊断准确性。 如果成功，我们的研究将有助于开发新的前列腺生物标志物，并可能更好地诊断，从而可能导致更好的临床结果和降低医疗费用。

DESCRIPTION (provided by applicant): Prostate cancer is a major health problem. Unfortunately, we do not as yet have effective methods for prostate cancer prevention. The best strategy that we have now for prostate cancer is early diagnosis followed by definitive treatment. This method significantly reduces prostate cancer mortality. The most widely used strategy for early diagnosis of prostate cancer includes measurement of prostate-specific antigen in serum. This method identifies men at high risk who, subsequently, are biopsied to confirm the diagnosis. Unfortunately, the test is not very powerful and approximately 5 patients have to be biopsied to detect 1 prostate cancer. Clearly, there is a need for development of more biomarkers for diagnosis of prostate cancer. We have recently discovered a new gene that belongs to the same family as PSA and has other characteristics which are also similar to PSA, i.e. the gene encodes for a secreted protease, the gene is regulated by androgens, is highly expressed in the prostate and the protein is secreted into the circulation. We speculate that the levels of the encoded protein, human kallikrein 4, may also be elevated in prostate cancer and that the measurement of hK4, in addition to PSA and other biomarkers, may significantly improve our ability to specifically diagnose early prostate cancer. In this grant application, we propose to develop the necessary technology for measuring human kallikrein 4 in serum and perform exploratory clinical studies to investigate if, indeed, the concentration of this biomarker is increased in prostate cancer and if its combination with other biomarkers can improve the diagnostic accuracy. If successful, our research will contribute to the development of new prostatic biomarkers and possibly, to better diagnosis which may lead to better clinical outcomes and reduced healthcare costs.