Proteomics for Cancer Detection

By David Olle

Proteomics is the study of all the proteins expressed by a given cell, tissue, or organism at a given time and under specific conditions. Proteomics is directly related to genomics, which is the study of all the genetic information in the chromosomes of a particular organism. Since genes direct the synthesis of proteins, the proteins present in the cell are dependent on the genome.

How can genomics be used to detect cancer?

A definitive diagnosis of cancer is largely based upon changes in cellular structure of tissue samples obtained by biopsy. Researchers have long recognized that cancer is due to changes in genes or gene activity, but difficulties in analytical methods have largely prevented taking advantage of this understanding until recently. The advent of the DNA microarray technology changed this situation, since it is now possible to rapidly analyze large numbers of genes in a patient’s tissue sample. By using this technology, researchers have detected several genes that are related to specific cancers.

However, the detection of genes by itself does not reflect the dynamics of what is going on in the cell. Proteins are the functional units of the cell, and their formation, concentrations, and interaction with other molecules have direct influences on the development of cancer. Proteomics is concerned with the entire network of proteins in the cell or tissue. This is essential, since the progression of cancer is largely due to aberrant signaling pathways, or how the cell receives a stimulus for growth or other activities.

Cancer proteomics can be characterized into expression proteomics and functional genomics. (5) Expression proteomics seeks to identify proteins that are differently displayed in tissues that can be used as markers for cancer detection, diagnosis, and in the development of novel treatments. Functional proteomics, on the other hand, is related to how proteins interact with each other, with DNA and RNA, or as components of larger complexes. This approach recognizes that proteins are part of a dynamic system, and that just identifying individual proteins is not adequate to explain their function.

Laboratory techniques to analyze proteins

The application of proteomics to cancer detection is dependent on laboratory techniques that are rapid, accurate, and reasonably economical. Traditional protein separation and detection techniques have been based on chromatography and gel electrophoresis, which do not satisfy these criteria.

However, the advent of the microarray technology has revolutionized the field. Following-up on techniques developed for DNA technology, many companies have developed their own versions of protein microarrays or “protein chips.” (2) The development of a protein chip is considerably more complex than its DNA counterpart, since proteins have a delicate three-dimensional structure that depends upon the physiological conditions in which they exist. Since protein function depends upon structure, the protein chips must maintain this structure. Protein microarrays are prepared by placing up to thousands of proteins as tiny spots onto a glass, metal or membrane surface. (1) Contrary to DNA fragments, proteins are quite variable in their physical properties, which make uniformity between spots difficult. A biological sample containing a mixture of proteins is then added to the “chip.” Proteins in the mixture will bind to corresponding proteins on the chip. In order to detect the bound proteins, the chip proteins may be labeled by fluorescence or radioactive elements. In another detection method, the protein’s molecular weight is determined by mass spectrometry.

Studies on cancer detection using proteomics (3, 4)

• Ovarian cancer – An early detection method for this cancer is vitally important, as ovarian cancer is usually not detected until it is too late. Studies at the University of California found that proteomic procedures distinguished between benign and malignant ovarian conditions with an accuracy of over 85%.
• Lung cancer – Three types of microchips were evaluated for usefulness in detecting lung cancer. Preliminary results revealed a protein that was enriched 5-fold to 10-fold in lung cancer cells.
• Colorectal cancer – Researchers used protein microchips in an attempt to understand the variability in response of cancer patients to treatment with nonsteroidal anti-inflammatory drugs, such as Celecoxib. Preliminary results indicate that protein signatures can be related to clinical outcome following chemoprevention treatment.
• Endometrial cancer – Researchers evaluated protein chips in an attempt to detect early-stage endometrial cancer. They found that ten proteins were overexpressed in endometrial cancer compared to normal tissues.

References:

1. Protein Chips Offer Powerful Method for Probing Protein Function. Howard Hughes Medical Institute, Sept. 8, 2000.

2. Lane, Laura. Protein Microarrays at the Cusp. The Scientist, Vol. 17, Issue 14, July 14, 2003.

3. Mariani, S. Clinical Proteomics: New Promises for Early Cancer Detection. Medscape General Medicine, Vol. 5, No. 2, 2003.

4. Mitchell, S. Proteomics Improving Cancer Detection. United Press International, Nov. 19, 2003.

5. Wu, W., Hu, W. and Kavanagh, J. Proteomics in Cancer Research. Int. J. Gynecol. Res. Vol. 12, pp. 409-423, 2002.

About the Author:

I have a very versatile background. After receiving my bachelors degree in Agriculture, I worked for a company doing research in animal nutrition and veterinary drug development.Writing up research reports and sections of New Drug Applications were important parts of my work.At this time I received a masters degree in biochemistry. After several years of consultant work in nutrition, I received a teacher's certificate, and taught chemistry at a community college and high school.In my current career in freelance science/medical writing, I have written two chapters and summaries for a Disease Prevention and Treatment book. I have written medical articles for an online company, and 67 articles on cancer treatments for Suite101.com. I have received two medical writing certificates from the American Medical Writers Association in order to strengthen my skills.I keep abreast of the latest developments in the medical fields, through searches,visiting appropriate sites,and e-mails. I am skilled in MS Office, Adobe Photoshop, and website design. I maintain my own website, www.eastshirecommunications.com, and publish a monthly newsletter.

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