22 biomarkers that provide a more accurate screening for prostate

Sep 22 2005

Researchers at the University of Michigan Comprehensive Cancer Center have identified a panel of 22 biomarkers that together provide a more accurate screening for prostate cancer than the current prostate specific antigen, or PSA, test.

The study appears in the current issue of the New England Journal of Medicine.

Researchers looked at blood samples taken from 331 prostate cancer patients prior to surgery, and from 159 control males with no history of cancer. They began by testing the samples against a library of 2,300 bacteriophage, organisms that express proteins on their surface, and were able to narrow the field to the 22 biomarkers that most often pinpointed the cancerous blood samples.

More than 230,000 men will be diagnosed with prostate cancer this year. Current screening methods involve a blood test to check for prostate specific antigen, an enzyme produced by the prostate. But the PSA test is controversial. A high level does not always indicate prostate cancer and some experts suggest a rise in PSA is more significant than a consistently high PSA. A high PSA level can also indicate benign prostate conditions.

"Initially, we envision this new test could be used as a supplement to PSA. A physician might suggest a patient with an elevated PSA have this test before a biopsy to better determine whether it's a cancerous or benign condition. In the future, I think this could replace PSA," says lead study author Arul Chinnaiyan, M.D., Ph.D., the S.P. Hicks Collegiate Professor of Pathology at the U-M Medical School.

In the current study, researchers first tested the blood serum samples of 39 men with prostate cancer and 21 controls to identify autoantibodies against prostate cancer. Cancer patients produce antibodies that fight against proteins that play a role in cancer. The researchers scanned 2,300 autoantibodies and initially narrowed it down to 186 that reacted with blood serum from the men with prostate cancer.

This discovery phase formed the basis for the next round of tests, in which 59 prostate cancer samples and 70 control samples were tested against the 186 autoantibodies. In this phase, the researcher identified a panel of 22 compounds that best distinguished the prostate cancer blood samples from the controls. Using these 22 markers, only two of 70 controls incorrectly tested positive for prostate cancer, and seven of 59 prostate cancer samples were falsely negative.

Next, the researchers validated their findings using the remaining 128 blood serum samples. They found eight of 68 controls and 11 of 60 prostate cancer samples were misclassified. This means 88 percent of the time, samples that were not cancerous were correctly identified and 81.6 percent of the time, samples that were cancerous tested positive.

"These 22 biomarkers appear to be the right number. If you used too many or too few, the accuracy went down a bit. Our findings held up when we tested the model on an independent set of blood serum samples," Chinnaiyan says.

The results proved to be more reliable at predicting cancer than prostate specific antigen, which is a single biomarker. PSA testing results in a false positive around 80 percent of the time, leading to unnecessary prostate biopsies. The normal range for the PSA test is less than 4.0 nanograms per milliliter (ng/mL) in most men. For men over 40 years old with a family history of prostate disease or for African-American men over 40 years old, some doctors suggest that a level higher than 2.5 ng/mL should be checked with more tests, because these two groups of men have an increased risk of prostate cancer.

The 22-biomarker test was reliable at identifying prostate cancer even in the PSA ranges of 4-10 ng/ml or 2.5-10 ng/ml, intermediate PSA scores that do not always suggest cancer. The study authors suggest the 22 biomarkers could be used for patients in this range to help determine whether to undergo a biopsy.

The new test requires only a routine blood draw for patients. Most blood-processing laboratories could easily be equipped to scan for these 22 biomarkers, Chinnaiyan says. Researchers are conducting further studies to validate the findings with a larger, community-based group of patients.