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

描述(申请人提供)：癌症生物标记物是特定的蛋白质，提供有关癌症的存在、进展、转移或复发的信息。生物标记物还可以帮助临床医生根据患者体内这些生物标记物的存在或数量做出治疗决定。理想的生物标记物是一种循环或分泌的蛋白质，可以在非侵入性方式从患者身上获得的血浆或尿液等样本中进行定量。由于不是所有形式的癌症都有临床证明的生物标志物，而且它们并不完全准确，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。本项目建议评估一种新的生物标记物，骨桥蛋白的N端蛋白水解性片段在乳腺癌和乳头状甲状腺癌患者中的应用，以测试其作为生物标记物的实用性。由于肿瘤是一个富含蛋白酶的环境，我们已经证明，骨桥蛋白的大部分被蛋白水解性修饰成更小的片段。尤其是N-末端片段是一种更高活性的蛋白质形式，因此在生物学上应该更好地代表肿瘤的进展。我们将测试骨桥蛋白N端片段是临床上有用的生物标志物的假设，方法是：1)开发和表征几种酶联免疫吸附试验，以特异性地定量人类血液中的这一片段，以及2)评估该分析在检测癌症、转移和治疗后疾病复发方面的有效性。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的过度表达有关，需要更多的生物标志物来评估疾病的进展。如果这一试点项目成功，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实用价值。 公共卫生相关性：该项目旨在开发一种新的癌症生物标记物，可以从人类血液中进行量化。这项研究的意义在于，我们可能会发现一种方法，帮助肿瘤学家早期诊断癌症，为评估治疗方案提供信息，并提供一种检测治疗后疾病转移或复发的方法。这些进展将通过改善对受影响患者的癌症护理来影响公共健康。

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.