CANDIDATE NEW BIOMARKER FOR BREAST CANCER DIAGNOSIS

减轻癌症负担的最佳方法之一是基于生物体液中生物标记物的测量进行早期诊断和监测的方法。这些生物标志物可能有助于早期发现和最终治疗的管理。激肽释放酶基因家族贡献了目前可用的最好的癌症标记物--前列腺特异性抗原。最近(1999)在作者的实验室中发现了一个新的激肽释放酶基因KLK-L2。这个生物标志物与PSA和其他激肽释放酶有很大的相似之处，是一种分泌型蛋白。在这项拨款申请中，假设新识别的基因KLK-L2可能编码一种潜在的生物标记蛋白，其在血液中的浓度可能在乳腺癌存在时发生变化。这一应用的主要目的是将新的激肽释放酶发展成为一种潜在的肿瘤标志物，适用于乳腺癌的诊断和监测。我们现在已经知道了新发现的激肽释放酶基因的完整基因组和cDNA序列。我们将开发适合于生物体液中候选生物标记物的重组蛋白、单抗和高灵敏免疫学检测方法。下一步，将进行初步临床研究，以检验新开发的生物标记物是否单独或与已知的生物标记物结合在一起，对乳腺癌的诊断、监测/预后和治疗选择具有任何价值。新发现的基因与已经成功的癌症生物标记物的特征和相似性以及其对乳腺的限制表达表明，新发现的基因具有成为临床有用的乳腺癌标记物的巨大潜力。

Among the best approaches for reducing the burden of cancer are methods for early diagnosis and monitoring, based on measurement of biomarkers in biological fluids. These biomarkers may facilitate early detection and administration of definitive treatment. The kallikrein gene family has contributed the best cancer marker currently available, prostate-specific antigen. A new kallikrein-like gene, KLK-L2 has been recently (1999) discovered in the author's laboratory. This biomarker exhibits significant similarities with PSA and other kallikreins and it is a secreted protein. In this grant application, it is hypothesized that the newly identified gene KLK-L2 may encode for a potential biomarker protein whose concentration in blood may be altered in the presence of breast cancer. The major aim of this application is to develop the new kallikrein into a potential tumor marker suitable for diagnosis and monitoring of breast cancer. We now know the complete genomic and cDNA sequence of the newly identified kallikrein gene. We will develop recombinant protein, monoclonal antibodies and highly sensitive immunological assays which will be suitable for measurement of the candidate biomarker in biological fluids. In the next step, preliminary clinical studies will be conducted to examine if the newly developed biomarker has any value, either alone or in combination with already known biomarkers, for breast cancer diagnosis, monitoring/prognosis and selection of therapy. Characteristics and similarities of the newly identified gene with already successful cancer biomarkers and its restricted expression to the mammary gland suggest that the newly identified gene holds significant potential for becoming a clinically useful breast cancer marker.