10 February 2010

Autoantibodies will help in the early diagnosis of cancer

Scientists from the University of Copenhagen have developed a new screening method that allows detecting cancer at the earliest stages of its development. The approach is based on the detection of autoantibodies in the patient's blood – molecules of immunoglobulins attacking the body's own tissues, which for some reason look "alien" to the immune system.

The authors demonstrated the ability of the new test to detect autoantibodies in about a third of blood samples from patients with newly diagnosed prostate, breast and ovarian cancer. At the same time, testing of control blood samples of healthy people gave negative results. The results of the work were published on February 2 in the preliminary on-line version of the journal Cancer Research in the article "Cancer Biomarkers Defined by Autoantibody Signatures to Aberrant O-Glycopeptide Epitopes".

Usually, the immune system begins to produce antibodies if a bacterial or viral pathogen enters the body. In some cases, this protective mechanism turns against the body itself, which leads to the development of autoimmune diseases such as rheumatoid arthritis and diabetes. When a malignant tumor appears in the body, autoantibodies begin to put a "black mark" on cancer cells, recognizing specific protein markers on their surface.

Currently, to diagnose certain types of cancer, doctors analyze the content of tumor-specific markers in the blood, such as prostate-specific antigen for prostate cancer and cancer antigen-125 for ovarian cancer. However, these protein molecules can also be synthesized by healthy cells, and their level increases in some other diseases, which significantly reduces the reliability of such testing. In addition, in the early stages of development, the tumor releases insignificant amounts of protein markers into the blood, which the liver quickly removes from the body.

According to one of the authors of the work, Hans Wandall, the immune system is able to detect even small amounts of antigens and attack them with specific autoantibodies even before they enter the liver. These immune agents circulate in the bloodstream longer and in larger quantities than their targets, which greatly facilitates their detection.

The researchers set themselves the task of developing a test to detect autoantibodies specific to a certain type of cancer antigens – mucin MUC1. (Mucins, from Latin mucus – mucus – glycoproteins that are part of the viscous secretions of mucous membranes.)

The micrograph shows the overexpression of polysaccharide structures (green) on the proteins of the surface of cancer cells. The cell nuclei are colored with a blue dye.

A large amount of MUC1 is characteristic of many types of malignant tumors, however, like other tumor markers, these molecules are also registered in other diseases. To increase the specificity of their test, the authors decided to create a combination of mucin and a more specific tumor antigen.

To do this, they chemically synthesized MUC1, to which they attached short polysaccharide chains similar to the chains attached to the proteins of the surface of cancer cells. (The surface proteins of normal cells are usually connected to much longer polysaccharide molecules.) The resulting complex compound was applied to the surface of microchips.

After that, the scientists collected blood serum samples from three groups of volunteers, each of which included 20 patients with prostate, breast or ovarian cancer, and passed them through the resulting microchips. Antibodies attached to the surface of microchips were detected using a fluorescent dye.

As a result, it turned out that the developed test allows detecting the presence of autoantibodies in the blood of 20-30% of cancer patients and does not detect them in the blood of healthy people. In the near future, the developers plan to work on increasing the specificity of the test by combining short polysaccharide structures with other tumor-associated proteins. They believe that over time, such a screening test may become a mandatory part of routine medical examinations.

Evgeniya Ryabtseva
Portal "Eternal youth" http://vechnayamolodost.ru based on the materials of TechnologyReview: An Early Warning System for Cancer.


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