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

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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.