Biomarker CCSA-2 May Provide Accurate Blood Test for Colorectal Cancer

A blood-based marker called colon cancer–specific antigen-2 (CCSA-2) may be an accurate indicator of colorectal cancer, according to preliminary research led by Johns Hopkins University in collaboration with the University of Pittsburgh and presented at the 5th annual Gastrointestinal Cancers Symposium, held January 25–27 in Orlando, Florida.

The goal of this research was to find an accurate, simple and noninvasive method for the early detection of colorectal cancer, similar to the prostate-specific antigen (PSA) blood test for prostate cancer. Other markers for colorectal cancer, including the fecal occult blood test and the carcinoembryonic antigen (CEA) test, are also found in patients with conditions other than cancer, and therefore lack specificity, resulting in false-positives in about 85% to 90% of cases for the fecal occult blood test and about 40% to 60% for the CEA test.

May Also Detect High-Risk Precancers

"Our goal when researching colorectal cancer biomarkers was to take a step back and try to understand the fundamental properties of the cancer cell," said Eddy S. Leman, phd, an instructor in the department of urology at Johns Hopkins Hospital. "The theory was that there must be a set of proteins that correlate with the changes that are seen when a cell becomes cancerous and are specific to colorectal cancer. With CCSA-2, we've found a biomarker that not only better detects the presence of colon cancer, but also may accurately indicate whether a patient has a high-risk precancerous condition."

Investigators analyzed 135 blood samples from patients who had undergone colonoscopies and had been diagnosed as normal (24%), having potentially precancerous growths (polyps: 19%; nonadvanced adenomas: 29%; advanced adenomas: 14%), or having colorectal cancer (14%). A control population of 125 people, made up of individuals with benign diseases or other types of cancer, was also included.

Dr. Leman and his colleagues previously demonstrated that the proteins colon cancer–specific antigen-3 and -4 (CCSA-3 and CCSA-4) can indicate the presence of colorectal cancer. The CCSA-2 immunoassay, however, is unique because in addition to detecting cancer, researchers noted a direct correlation between the level of biomarker in the blood and the size of adenomas: The higher the level of biomarker in the blood, the larger the growth; the highest levels of the biomarker indicated the presence of colorectal cancer. The researchers could thus distinguish patients who had colorectal cancer or advanced adenomas from those who had nonadvanced adenomas, low-risk polyps or normal colons. CCSA-2 also had a lower rate of false-positives than CCSA-3 and CCSA-4.

The test had an overall specificity of about 80% and a sensitivity of 91%. Based on these results, the next step is to validate the findings with larger groups of patients at a greater number of research institutions.