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

描述(申请人提供)：前列腺癌是一个主要的健康问题。不幸的是，到目前为止，我们还没有预防前列腺癌的有效方法。我们现在对前列腺癌的最好策略是早期诊断，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。最广泛使用的前列腺癌早期诊断方法包括测定血清中的前列腺特异性抗原。这种方法识别高危男性，随后对他们进行活组织检查以确认诊断。不幸的是，这项测试并不是很有效，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，有必要开发更多用于前列腺癌诊断的生物标志物。 我们最近发现了一个新的基因，它与PSA属于同一家族，并且具有与PSA相似的其他特征，即该基因编码一种分泌型蛋白酶，该基因受雄激素调控，在前列腺中高表达，蛋白质分泌到循环中。我们推测，编码蛋白人激肽释放酶4的水平在前列腺癌中也可能升高，并且除了PSA和其他生物标志物外，HK4的测量可能显著提高我们特异性诊断早期前列腺癌的能力。在这项拨款申请中，我们建议开发必要的技术来测量血清中人激肽释放酶4，并进行探索性临床研究，以调查前列腺癌中该生物标记物的浓度是否确实增加，以及它与其他生物标记物的结合是否可以提高诊断的准确性。 如果成功，我们的研究将有助于开发新的前列腺生物标记物，并可能有助于更好的诊断，从而可能导致更好的临床结果和降低医疗成本。

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.