Proteomic profiling from human samples: the body fluid alternative

Proteomics is one of the technologies rapidly changing our approach to drug development. The applications of proteomics, particularly with reference to analysis of body fluid samples, will be described. Proteomic analysis involves the systematic separation, identification and characterisation of proteins present in a biological sample. By comparing the proteins present in diseased samples with those present in normal samples, it is possible to identify changes in expression of proteins that potentially may be related to organ toxicity. Proteomics is regarded as a sister technology to genomics. Although the pattern of gene activity will be abnormal in a tissue with a pathological lesion, there can be a poor correlation between the level of activity of different genes and the relative abundance within the tissue of the corresponding proteins. This is especially true where the mode of action of the test material interferes with protein synthesis and/or post translational modification. Consequently, the information about a pathological process that can be derived at the level of gene activity is incomplete. Proteomics has now made it possible to analyse proteins using high throughput, automated techniques. Although both mRNA and proteomic profiling can be applied to tissue samples, analysis of body fluids (e.g. serum, urine, CSF, synovial fluid) is restricted to proteomics. In these cases the protein composition is derived from many tissues and processes. Proteomic analysis can yield information on disease processes and potential response to treatment. Examples will be presented of the identification of surrogate markets for hepatocellular carcinoma, breast cancer, from cerebrospinal fluid in humans and gentamicin toxicity in the rat. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.