Protein Microarray Finds Predictors for Breast Cancer

A blood test, that uses a microarray designed to search for proteins, recognizes the antibodies from cancer patients, but not from healthy women.

Protein microarrays display thousands of different candidate proteins lined up in rows and columns on a single microscopic slide. These proteins including autoantibodies can be measured in the blood and used to reveal the presence of a hidden cancer.

Scientists from the Biodesign Institute at Arizona State University (Tempe, AZ, USA), used a novel protein microarray technology, called Nucleic Acid Protein Programmable Array (NAPPA), to screen for biomarkers for breast cancer. To detect autoantibodies, they probed NAPPA microarrays expressing 4,988 candidate tumor antigens with sera from patients with early stage breast cancer (IBC), and the bound immunoglobulin G (IgG) was measured. To narrow down the list of candidates, several successive screens were performed that compared the immune responses in women with IBC, those without cancer, and those with benign abnormalities in their breasts. The patients and controls were also matched for age and location.

Three phases of screens were performed, using increasingly rigorous statistical selection standards that narrowed down the number of potential biomarkers candidates from 5,000 to 761, which showed any measurable difference between healthy and disease populations, and then reduced to 119, which showed a clear statistical difference. Finally, these 119 were tested in a blinded study to find the final 28 biomarkers. The group not only looked at how each individual biomarker fared during the screening, but also how the entire panel of biomarkers worked together.

This was the first time the group has utilized NAPPA technology to identify the parts of the immune response that are activated during cancer, and the first serum biomarker panel developed for the discrimination of benign breast disease from invasive breast cancers. The group confirmed that many of the candidate biomarkers have also been described as important in breast cancer-tumor biology and pathology.

Joshua LaBaer, MD PhD, director of the Biodesign Institute, said, "We were surprised at how hard it is to find biomarkers like this. The changes are subtle and rare, which is a real warning shot to those investigating breast cancers. The key is a team approach that combines many different types of scientific expertise to tackle the problem." The study was published in October 2010, in the Journal of Proteome Research.

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