Discovery of New Biomarkers of Cancer Using Proteomics Technology

Catherine      P. Riley; Jiri      Adamec

Abstract

The medical community would benefit tremendously from a single test to screen for multiple cancers simultaneously with results that would allow the physician to tailor treatment to the individual. An ultimate goal is to utilize the same test to monitor treatment efficacy and prognosis. Critical components of such tests are likely to be biomarkers, molecules that indicate normal or pathogenic biological processes. The ability to systematically examine disease at the molecular level with high-throughput technologies, such as genomics and proteomics, has opened up new and exciting possibilities for biomarker discovery. Microarray analyses for example, have recently revealed gene expression ‘signatures’ of breast cancer. Additionally, recent advances in proteomics technology provide powerful analytical tools for the discovery and detection of differentially expressed and post-translationally-modified candidate protein biomarkers in tumors and blood. It is expected that new molecular markers will facilitate the move away from population based and toward personalized medicine. Unfortunately, the discovery of sensitive and specific biomarkers for human cancer has been hindered by undefined genetic and environmental heterogeneity. Large numbers of human clinical specimens may overcome these obstacles, but these are difficult to obtain. Furthermore, identification of low abundance proteins in plasma has been proven to be a daunting task due to the vast dynamic range of protein concentrations in the plasma proteome. These issues, coupled with the enormous volume of resulting data, create a bottleneck for identification of relevant biomarkers. An attractive alternative that acknowledges the shortcomings of the current technologies yet is still a comprehensive approach for biomarker discovery is to employ comparative studies in less complex biofluids followed by verification with targeted mass spectromerty analyses for differential expression in human disease plasma.

Keywords: Biomarker, cancer, diagnosis, proteomics, validation, computer tomography, transferrin, mass spectrometry, gel electrophoresis, Peptide Mass Fingerprinting, high performance liquid chromatography