NEW SCREENING FOR PROSTATE CANCER SHOWS DRAMATIC SUCCESS IN LAB TESTS
Findings reported in July issue of The Journal of Urology
June 14, 2004
WORCESTER, Mass. — A prostate cancer screening test developed at the University of Massachusetts Medical School achieved a 94 percent success rate in a blinded study of serum samples from healthy men and those who had been diagnosed with prostate cancer through a traditional biopsy.
The results of the study are published in the July 2004 issue of The Journal of Urology and indicate this technology may eventually yield a rapid, highly accurate, clinical screening test to replace the current PSA test for prostate cancer. “Not only did we detect the cancer with a high degree of accuracy, we’re able to differentiate between subtypes of tumors,” said Shuk-Mei Ho, PhD , professor of Surgery, Cell Biology and Physiology and Director of Urologic Research and Translational Research for the Department of Surgery at UMMS, whose lab developed the screening technology. “Early detection of prostate cancer is important because when it’s caught early the survival rate is almost 15 years. But when the disease is caught in the advanced stage and has spread beyond the prostate, the survival rate is very poor. So we’re hopeful this screening technology will have important clinical uses in the future, both by catching the cancer early, and helping to identify which cancers are more aggressive,” Dr. Ho said.
Prostate cancer is now the most frequently diagnosed malignancy in American men, with 220,000 new cases and nearly 30,000 deaths in 2003. As baby boomers age, those numbers are expected to increase. Currently, there is just one marker used to test men for prostate cancer—prostate specific antigen (PSA). A rising PSA level in the blood stream can indicate cancer, but the PSA test has high false-positive and high false-negative rates, so significant efforts are underway at UMMS and other institutions to develop a more accurate test to detect prostate cancer.
The new screening platform developed at UMMS uses mass spectrometry—a process that measures the mass and electrical charges of molecules in a sample to identify unknown substances and quantify known substances. With mass spectrometry, Ho’s team determined the mass-to-charge ratios of hundreds of proteins that are found in the sera of men diagnosed with prostate cancer. The mass spectra of the sera samples were then digitized and processed by software package Ho’s team configured for the screening process. The results of the computer analysis were then correlated with the known clinical profiles and outcomes of the patients. “Instead of using only PSA level, the combination of changes in the abundance of multiple proteins are used to predict cancer for each patient and classify their disease stage. That allows us to not only identify prostate cancer with a higher level of accuracy, but also to identify subtypes of prostate cancer,” Ho said.
In the study published in the Journal of Urology, Ho’s lab focused on 36 “protein peaks” in the sera that characterized the presence of prostate cancer. The first tests were done on 48 serum samples, where the diagnoses of the patients were known up front. Those 48 samples were used to refine and “train” the computer model used to analyze the protein data from the serum. Following that, Ho’s team tested168 blind serum samples, meaning the researchers did not know which samples came from healthy men versus those taken from men diagnosed with prostate cancer via biopsy. In that second set, the testing platform accurately diagnosed the cancer, or lack thereof, in 158 cases— a 94 % success rate. Of the remaining 10 cases, one was a false positive, four were false negatives and five were inconclusive.
Ho’s team is now testing the new process on a much larger scale, using hundreds of serum samples from labs across the country. If the process continues to perform well, Ho expects the research will lead to a more reliable and informative clinical prostate screening that will help catch the disease earlier and target the most effective treatment. “Eventually, we hope this test can be refined so it is a very simple, inexpensive blood test, perhaps even a urine analysis test,” Ho said. “We’ve got more work to do, but so far, we’re pleased with the progress.”
In addition to her own lab work, Dr. Ho is co-director of the Genitourinary Oncology Program at the UMass Memorial Cancer Center, which brings together researchers and clinicians to help translate basic science advances into clinical applications for cancer treatment.
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The University of Massachusetts Medical School is one of the fastest growing academic health centers in the country and has built a reputation as a world-class research institution, consistently producing noteworthy advances in clinical and basic research. The Medical School attracts more than $154 million in research funding annually, 80 percent of which comes from federal funding sources. Research funding enables UMMS scientists to explore human disease from the molecular level to large-scale clinical trials. Basic and clinical research leads to new approaches for diagnosis, treatment and prevention of disease.
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