Advances in mass spectrometry-based clinical biomarker discovery

摘要

The greatest unmet needs in biomarker discovery are those discoveries that lead to the development of clinical diagnostic tests. These clinical diagnostic tests can provide early intervention when a patient would present otherwise healthy (e.g., cancer or cardiovascular disease) and aid clinical decision making with improved clinical outcomes. The past two decades have seen significant technological improvements in the analytical capabilities of mass spectrometers. Mass spectrometers are unique in that they can directly analyze any biological molecule susceptible to ioniza-tion.The biological studies of human metabolites and proteins using contemporary mass spectrometry technology (metabolomics and proteomics, respectively) has been ongoing for over a decade. Some of these studies have resulted in exciting insights into human biology. However, relatively few biomarkers have been translated into clinical tests. This review will discuss some key technological developments that have occurred over this time with an emphasis on technologies that will create new avenues for biomarker discovery. Laboratory medicine has a tremendous impact on clinical decision making. Currently, most routine chemistry tests utilize spectrophotometric or immunologic detection schema. Mass spectrometry (MS) typically provides much greater analytical specificity relative to these methods. Mass spectrometry has been used routinely in the clinical laboratory, primarily in the context of toxi-cological testing and therapeutic drug monitoring. The success of mass spectrometry in these clinical testing arenas is juxtaposed by a promise of a golden age of biomarker discovery. This review will present a contemporary perspective on the challenges and opportunities for biomarker discovery as well as speculate on their future clinical applications. It will also address how technical innovation has instilled new promise for mass spectrometry based biomarkers, including both protein-based and small molecule-based biomarkers. Finally, it will present the foundational terminology necessary for evaluating biomarkers in a clinical context.