Proteomics in Biomarker Discovery

He QY, Chiu JF. Proteomics in biomarker discovery and drug development. J Cell Biochem 2003 89 868-886. 

Ho L, Sharma N, Blackman L, Eesta E, Reddy G, Pasinetti GM (2005) Prom proteomics to biomarker discovery in Alzheimer s disease. Brain Res Brain Res Rev 48 360-369. 

In proteomics and biomarker discovery, complex mass spectra from single protems, protein mixtures, or protein digests are obtained. Data systems exist that aid in characterization of spectral data to identify such properties as intact protein mass, amino acid subsequences, and post-translational modifications. Fragmentation information can also be compared with peptide databases to identify structural mutations that may be present. 

SILAC-based proteomics approach was successfully used to identify a total of 63 differentially expressed proteins between a HepG2 human hepatoma cell line and an immortal hepatic cell line L02 [83]. Among these differentially expressed proteins, phosphoglyc-erate mutase was found highly upregulated and might play important role in hepatocarcinogenesis, which demonstrated the remarkable power of this SILAC platform in biomarker discovery. 

Bichsel, V.E., Liotta, L.A., and Petricoin, E.F., 3rd, (2001) Cancer proteomics from biomarker discovery to signal pathway profiling. Cancer J 7, 69-78. Chuaqui, R., Cole, K., Cuello, M., Silva, M., Quintana, M.E., and Emmert-Buck, M.R. (1999) Analysis of mRNA quality in freshly prepared and archival Papanicolaou samples. Acta Cytol 43, 831-6. 

Meistermann H, Norris J, Aerni H, et al. Biomarker discovery by imaging mass spectrometry transthyretin is a biomarker for gentamicin-induced nephrotoxicity in rat. Mol. Cell. Proteomics 2006 5 1876-1886. 

Melle, C., Ernst, G., Schimmel, B., Bleul, A, Koscielny, S., Wiesner, A., Bogumil, R., Moller, U., Osterloh, D., Halbhuber, K.J., and F. Von Eggling, 2003, Biomarker Discovery and Identification in Laser Microdissected Head and Neck Squamous Cell Carcinoma with ProteinChip(R) Technology, Two-dimensional Gel Electrophoresis, Tandem Mass Spectrometry, and Immunohistochemistry. Mol Cell Proteomics. 2(7) 443-52. 

After xenobiotic/toxin exposure, differentially expressed proteins are identified by the comparison of SELDI spectra from control and treated samples. By combining groupwise statistics with N-fold regulations, single biomarkers (m/z) can be selected. As to be expected from the complexity of the proteome, in many cases no single marker will be able to discriminate between the groups. Rather, a complex pattern of multiple markers will be acquired (Figure 8). Discovery of such markers/pattems can be successful by application of multivariate statistics methods on the data set. However, for the identification of specific protein expression patterns bioinformatics tools are... 

Biomarker Discovery in Renal Cell Carcinoma Applying Proteome-Based Studies in Combination with Serology... 

The continued use of proteomics, as described in this review, should result in the discovery of new diagnostic and/or prognostic biomarkers, in addition to those already identified in the referenced studies in this chapter, facilitating the identification of potential drug targets for the development of new therapeutic approaches for combating heart and cardiovascular disease. 

Recent advancements in genomics and proteomics have generated considerable interest in the discovery and validation of biomarkers in mechanism-based drug development [69-71], These advances have been welcomed to reduce the cost, increase success rates, and accelerate timelines in the drug discovery and development process. Herein, a brief overview of the application of biological markers in early discovery, development, toxicological assessments, and efficacy studies in humans is presented. 

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