Although cancer antigen CA125 (MUC16) is an established biomarker for ovarian cancer, the sensitivity and specificity of existing detection methods are inadequate. Here, we propose to combine the extraordinary specificity of vibrational spectroscopy with the molecular amplification of plasmonic nanoparticles to address this diagnostic problem. Specifically, we will design, synthesize and characterize novel nanostructured surface enhanced Raman scattering (SERS) reporters and subsequently use the SERS-based platforms for ultra-sensitive detection of free CA125 in blood serum to predict disease behavior. Further, a SERS microscopy system will be developed to image, for the first time, the specific surface interactions of CA125 antigen with receptors in blood leukocytes to understand what mucin/leukocyte immunologic interactions drive ovarian cancer elimination, equilibrium, or escape.