Identification of proteins released by follicular lymphoma-derived cells using a mass spectrometry-based approach

The recent advent of mass spectrometry-based methodologies for the analysis of complex protein mixtures opens new opportunities for the discovery of biomarkers that may aid in the diagnostic work-up of cancer. Follicular lymphoma (FL) is the most common form of low-grade non-Hodgkin lymphoma in the Western Hemisphere. Identification of tumor markers that facilitate early disease detection would be a significant advance in the management of FL. We have employed a strategy that entailed propagation of a follicular-derived cell line in serum-free media, protein extraction, and reverse-phase liquid chromatography, with subsequent electrospray ionization and tandem mass spectrometry analysis for the identification of proteins that are released by FL. Using a two-peptide minimum per protein and standard criteria, 209 proteins (5.6% maximum predicted error rate) released from the FL cells were identified. The released proteins included several growth factors, cytokines, acute phase reactants and cellular components previously known to be present in FL cells. Importantly, a greater proportion of proteins previously unassociated with FL were identified with high statistical confidence. Our studies provide a list of proteins, which may be candidates for early screening, diagnosis and therapeutic monitoring of patients with a suspected or biopsy-confirmed diagnosis of FL.