A novel osteopontin fragment as a diagnostic/prognostic cancer plasma biomarker

描述（由申请人提供）：癌症生物标志物是提供有关癌症存在、进展、转移或复发信息的特定蛋白质。生物标志物还可以根据患者体内这些生物标志物的存在或数量，帮助临床医生做出治疗决定。理想的生物标志物是一种循环或分泌的蛋白质，可以在血浆或尿液等样品中以非侵入性方式进行量化。由于并非所有形式的癌症都有临床证明的生物标志物，而且它们也不完全准确，因此开发新的生物标志物与现有的生物标志物结合使用是很重要的。本项目拟对乳腺癌和甲状腺乳头状癌患者的骨桥蛋白n端蛋白水解片段作为一种新的生物标志物进行评估，以检验其作为生物标志物的实用性。由于肿瘤是一个蛋白酶丰富的环境，我们已经表明，大部分骨桥蛋白被蛋白水解修饰成更小的片段。特别是n端片段是一种高度活跃的蛋白质形式，因此生物学上应该是肿瘤进展的更好代表。我们将通过以下方法来验证骨桥蛋白N端片段是一种临床有用的生物标志物的假设：1)开发和表征几种酶联免疫吸附试验，以特异性地量化人类血液中的该片段；2)评估该试验在检测癌症、转移和治疗后疾病复发方面的功效。我们的患者群体将包括乳腺癌和乳头状甲状腺癌，这两种疾病都与骨桥蛋白过表达相关，需要额外的生物标志物来评估疾病进展。如果这个试点项目取得成功，我们将确定一种急需的非侵入性生物标志物，它将在人类癌症的诊断和治疗中具有临床效用。

DESCRIPTION (provided by applicant): Cancer biomarkers are specific proteins that give information about the presence, progression, metastasis, or recurrence of cancer. Biomarkers can also assist the clinician in making decisions about treatment, based upon the presence or amount of these biomarkers in the patient. The ideal biomarker is a circulating or secreted protein that can be quantified in samples such as plasma or urine that are obtained from the patient in a non-invasive manner. Since not all forms of cancer have clinically proven biomarkers, and since they are not completely accurate, it is important to develop new biomarkers for use in combination with existing ones. This project proposes to evaluate a novel biomarker, an N-terminal proteolytic fragment of osteopontin in breast cancer and papillary thyroid carcinoma patients, to test its utility as a biomarker. Since the tumor is a rich environment for proteases, we have shown that much of the osteopontin protein is proteolytically modified into smaller fragments. The N-terminal fragment in particular is a more highly active form of the protein, and thus biologically should be a better representation of tumor progression. We will test the hypothesis that this N- terminal fragment of osteopontin is a clinically useful biomarker, by: 1) developing and characterizing several enzyme-linked immunosorbent assays to specifically quantify this fragment in human blood, and 2) evaluating the efficacy of the assay in detecting cancer, metastasis, and recurrence of disease after treatment. Our patient population will consist of breast cancer and papillary thyroid cancer, both of which are diseases that have been associated with the overexpression of osteopontin, and are in need of additional biomarkers to assess disease progression. If this pilot project is successful, we will have identified a much-needed non-invasive biomarker that will have clinical utility in the diagnosis and treatment of human cancer. PUBLIC HEALTH RELEVANCE: This project aims to develop a novel biomarker of cancer that can be quantified from human blood. The significance of this study is that we will potentially discover a means to assist the oncologist in the early diagnosis of cancer, provide information to evaluate treatment options, and provide an assay to detect metastasis or recurrence of disease following treatment. These advances will impact public health by improving cancer care for affected patients.