MSACL Conference Schedule

Discovery and Validation of a Cancer Biomarker: From Technology Development to Clinical Application
Mon 4:00 PM - Session: Proteomics
Sushmita "Mimi" Roy
Discovery and identification of disease biomarkers that stand up to clinical validation has been a scientific challenge. We have developed a proprietary liquid chromatography-mass spectrometry quantitative label-free proteomic profiling platform with attention to robustness, reproducibility and sensitivity. The technology platform is amenable to a variety of body fluids and tissues from human and animal studies and has successfully been used to discover biomarkers for drug development, theranostic and diagnostic purposes. In this presentation, the fundamental features of this platform will be outlined highlighting precautions required to obtain quality-controlled complex proteomic data. As an example, a study will be presented on finding diagnostic markers of brain lymphoma, recently published in the Journal of Clinical Oncology 26, pp 96-105 (2008). Label-free differential proteomic analysis based on two-dimensional liquid chromatography-mass spectrometry (2D-LC-MS) and identification of more than 500 proteins in cerebral spinal fluid (CSF) proteins was used to distinguish B-cell CNS lymphoma from benign conditions. In this study not only were a set of markers replicated in two independent sets of patients in two studies conducted a year apart, but one of the discovered markers was subsequently cross-validated for 100 subjects using an ELISA assay. The marker was shown to have diagnostic and prognostic value. Our findings demonstrate for the first time that proteomic analysis of CSF yields individual biomarkers with greater sensitivity than CSF cytology in the identification of cancer. We propose that the discovery of CSF protein markers will facilitate early and noninvasive diagnosis in patients with focal brain lesions, eventually eliminating common brain biopsy as well as providing improved surrogates of prognosis and treatment response in CNS lymphoma and other cancers originating in, or metastasizing to, the brain.
Email: [email protected]