Tissue Proteomics and Metabolomics: An Excellent Start and a Promising Future
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roteomics continues to advance on many fronts. More sophisticated sample preparation methods, such as the depletion of abundant proteins, phosphoprotein enrichment, and metabolite extraction, continue to be developed. In addition, more advanced instrumentation, such as high-sensitivity mass spectrometers and the emergence of tissue arrays, has enabled a greater depth of the proteome to be surveyed. Furthermore, advances in bioinformatics have continued to allow investigators to query and assimilate the very complex data sets that result from proteomic analyses. Combining all of these developments has greatly increased the breadth of biological specimens that are now amenable to proteomic discovery. Although much of the focus of clinical proteomics and metabolomics, in particular, has centered on serum and plasma in the recent past, the analysis of tissues offers several important advantages. For example, the direct study of tumor tissues provides a description of molecules as they exist within the context of their surroundings. In the field of biomarker discovery, the greatest chance of discovering a novel biomarker resides in the study of the damaged tissue because it seems likely that the concentration of the potential biomarker would be greatest at this location. Unfortunately, proteomic analysis of tissues also presents a few difficulties. Tissues are heterogeneous (comprising multiple cell types). Tissues have also been historically difficult to obtain in sufficient quantities, particularly when they will be used in comparative studies measuring changes in protein abundances. These properties have caused a majority of proteomic and metabolomic investigations to be conducted with cultured cells, which have a more defined population and can be obtained in larger quantities than in vivo tissues. Maybe no specimen type has benefited more from the developments made in the areas of sample preparation and technology advancement than tissues. Although sensitivity, dynamic range, and tandem mass spectrometry (MS2) dutycycle enhancements have affected almost every sample that is analyzed with MS, their impact has been felt especially in tissue proteomics and metabolomics. These enhancements have enabled more proteins to be identified from increasingly smaller amounts of sample. For example, the pioneering work
10.1021/pr900157d
© 2009 American Chemical Society
of Richard Caprioli and colleagues at Vanderbilt University has allowed researchers to image entire tissue sections to reveal patterns of proteins or monitor specific molecules and their metabolites within these samples. Not only are entire tissue sections amenable to in-depth analysis but specific cell populations also can be isolated. With laser-capture microdissection, investigators can readily analyze small subpopulations of cells within a tissue with MS. Recent sample preparation developments have also made formalin-fixed tissues amenable to proteomic analysis with MS, opening up a vast archive of clinically important samples for interrogation. On the technology side, the developments are not limited to MS. Tremendous strides have been made in advanced NMR methods for surveying metabolomes extracted from both animal and plant tissues. Investigators have taken standard techniques such as immunohistochemistry and immunoblotting and designed high-throughput microarrays that can concurrently interrogate hundreds of proteins in a variety of different tissue sections within the same study. Looking back over the contributions that a particular field of science has made to peer-reviewed literature is a good indication of its progress. A simple PubMed search shows that the topic of tissue proteomics has been part of the literature for approximately a decade now. Of this contribution, ∼60% of the peer-reviewed articles have been published in the past 2 years. Although the field of tissue metabolomics is not as heavily populated, the same publication trend is observed. If we consider this trend in combination with the innovative studies presented in this special issue of JPR, it is easy to conclude that the field has not yet reached its full potential, and many more exciting developments, including the progression of tissue proteomics and metabolomics as routine clinical tools, are still to come. Finally, the editors wish to thank all of the authors who have contributed their time to present not only their research, but also their insights. Without each of you this special issue would not be possible. TIMOTHY D. VEENSTRA and MING ZHOU SAIC-Frederick, Inc.
Journal of Proteome Research • Vol. 8, No. 4, 2009 1617
