Proteomics and cancer diagnosis 2/2/03. By Richard Twyman Large-scale protein analysis can identify cancer-related proteins that can be used as diagnostic markers and perhaps as targets for drug development.

One of the major application of proteomics is the diagnosis and treatment of human diseases. The main proteomic technology platform, two-dimensional gel electrophoresis, is used to separate complex protein mixtures allowing individual protein spots on the gel to be identified by mass spectrometry.

If two related samples are compared, for example some normal healthy tissue and a disease sample, differences in the abundances of particular proteins may be evident. A protein present in the disease sample but not in the healthy sample may be a useful drug target. It may represent an aberrant form of a protein or a normal protein expressed at an unusually high level or in the wrong place. Even if the protein is unsuitable as a drug target, it may still be useful as a diagnostic marker.

Although proteomics is a relatively new research area, there have already been some promising results in the diagnosis of cancer. For example, proteins have been identified that can be used to diagnose breast cancer, colon cancer and bladder cancer. A protein called stathmin has been identified that is expressed at unusually high levels in cases of childhood leukaemia.

Interestingly, the stathmin protein is phosphorylated in cancer patients – it has an additional phosphate group added to it. Many proteins are modified by phosphorylation after they are synthesized. Such modifications change the chemical properties of the protein allowing the phosphorylated and non-phosphorylated forms to be separated by two-dimensional gel electrophoresis. In the case of stathmin, only the phosphorylated form is associated with childhood leukaemia. This emphasises the importance of proteomics in disease diagnosis, because a change in protein modification associated with cancer cannot be detected using DNA arrays.

In the case of bladder cancer, proteomics analysis has identified several keratin proteins that are expressed in different amounts as the disease progresses from the early transitional epithelium stage to full blown squamous cell carcinoma.

The measurement of keratin levels in bladder cancer biopsies can therefore be used to monitor the progression of the disease. Another protein, psoriasin, is found in the urine of bladder cancer patients and can be used as an early diagnostic marker for the disease. This provides another example of how proteomics, but not DNA arrays, can be used in cancer diagnosis. Urine, in common with most bodily fluids, contains proteins but no RNA.

Image credit: Dr David Becker