Proteomics of body fluids

In this thesis we present newly developed methods for biomarker discovery. We applied these methods to discover biomarkers of leptomeningeal metastasis (LM) in the cerebrospinal fluid (CSF) from breast cancer patients and in serum from patients with prostate cancer. Early diagnosis of LM remains challenging because 25% of CSF samples test false negative at first cytological examination. In addition, the sensitivity and specificity of magnetic resonance imaging (MRI) in diagnosing LM in solid tumors are approximately 75%. Early diagnosis and initiation of treatment of LM are essential to prevent neurological deterioration. We therefore set out to find biomarkers to increase the accuracy of early diagnostic testing in LM. For prostate cancer a biomarker in the form of prostate specific antigen (PSA) is available. The specificity of this marker is however rather poor, in screening studies like the European Randomized study of Screening for Prostate Cancer (ERSPC) 75% of men with an elevated PSA level > 3 ng/ml are false positive. Resulting in a group of men that undergo unnecessary treatment with a risk of complications including impotence and incontinence. New markers in addition to PSA could help to reduce the large number of false positive diagnosed patients and to predict the course of the disease.

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