Mass Spectrometry Based Proteomics in Cancer Research

Abstract

Proteomics has become an important component of biological and ­clinical research. Numerous proteomics methods have been developed to identify and quantify the proteins present in biological and clinical samples (Gerber et al., Proc Natl Acad Sci U S A 100:6940–6945, 2003; Ong et al., Methods 29:124–130, 2003). Differences among cell types or treatment groups have been used to identify cellular functions and pathways affected by disease or perturbations (Wright et al., Genome Biol 5:R4, 2003; Durr et al., Nat Biotechnol 22:985–992, 2004), new components and changes in the composition of protein complexes and ­organelles (Andersen et al., Nature 426:570–574, 2003; Blagoev et al., Nat Biotechnol 21:315–318, 2003; Ranish et al., Nat Genet 36:707–713, 2004), and putative disease biomarkers (Marko-Varga et al., J Proteome Res 4:1200–1212, 2005). Despite widespread success, the application of these approaches to discovery of relevant protein markers from clinical samples has been hampered by sample complexity and variability. To begin to broach this challenge, complex experimental protocols for enrichment, separation, and quantification have been developed for selective or comprehensive proteome analysis. In this chapter, we describe techniques for enrichment, separation, quantification, fundamentals of mass spectrometry, and the computational analysis of data generated by these processes within the context of using these approaches for asking and answering biologically and clinically important questions.