Clinical proteomics in molecular genetic pathology

Patient tissue specimens contain a wealth of potential diagnostic molecular descriptors. Clinical proteomics is a field that combines components of classical protein detection technologies with new technologies to create high-throughput assays that effectively utilize the proteomic information available in the limited sample volumes that are most commonly obtained in the clinical setting. Protein microarrays provide a means for measuring the levels of disease-related proteins extracted from patient tissues, and our laboratory developed the reverse-phase microarray to define the contribution of specific protein activation states to various cancer disease processes. Preservation and stabilization of the in vivo protein signaling architecture is critical for clinical applications, and new tissue fixatives have been recently developed to minimize sources of preanalytical variables. Mass spectrometry, a highly sensitive proteomics tool, is now widely used as an analytical method to discover and catalog disease-related proteins in solid tissues and body fluids such as plasma, serum, and cerebrospinal fluid. Peptidomic and low-molecular-weight proteomics is an important emerging niche in protein biomarker research that requires both analyte concentration and size exclusion simultaneously. New core-shell hydrogel nanoparticles have been developed for one-step, high-throughput low-molecular-weight biomarker concentration, size filtration, and preservation for downstream mass spectrometry analysis and biomarker discovery. Using these new methods, the proteomics field is poised to greatly accelerate tissue and body fluid biomarker discovery, validation, and clinical implementation.