Recent Advances in Mass Spectrometry‐Based Proteomic Methods for Discovery of Protein Biomarkers for Complex Human Diseases

As advanced proteomic technologies have been developed, huge amounts of proteomic data have been generated from a broad spectrum of patient tissue and body fluid samples collected under various disease conditions. From these data, proteomic biomarkers that can serve as indicators of disease states have been searched for numerous diseases. To discover reliable protein biomarkers, high-throughput proteomic platforms have been developed, including two-dimensional gel electrophoresis, mass spectrometry (MS)-based proteomic analysis, and protein–antibody microarrays. Of these platforms, liquid chromatography–tandem MS (LC–MS/MS) analysis has been widely used for discovery of protein biomarkers due to its high sensitivity in analytical capability and large dynamic ranges of detection. Before LC–MS/MS analysis, exhaustive fractionations of complex protein samples are often employed to improve the depth of proteome profiles during the discovery phase of protein biomarkers. Moreover, LC–MS/MS analysis provides the high-throughput capability sufficient for verification of protein biomarker candidates selected from the discovery phase in large cohorts of clinical samples before their clinical use. Here, we summarize recent advances in MS-based proteomic methods applied for the discovery of protein biomarkers.