New Blood-Test Evaluated to Identify Women at Risk for Ovarian Cancer

Prior studies have suggested that glycans are differentially expressed in patients with ovarian cancer versus controls. A team based at the University of California Davis Comprehensive Cancer Center (Sacramento, CA, USA) has discovered a blood-based glycan biomarker panel that may identify women as risk for epithelial ovarian cancer (EOC), and have verified that glycans can be used to detect this disease. In their report, published in the journal Cancer Epidemiology, Biomarkers & Prevention, March 7, 2014 (online ahead of print), Kim et al. describe their glycomics approach and results.

“This is one of many papers we’ve done to see if glycans can distinguish between women who have ovarian cancer and those who don’t,” said study leader Gary Leiserowitz, chief of the Division of Gynecologic Oncology; “So far, the results have been consistent and promising.” Since glycans are often altered when patients have cancer, by measuring these changes the team hopes to develop a simple blood test that will detects OC very early.

The team conducted a series of experiments to ensure their glycan measurements were indeed detecting cancer. “You have to do these incredibly rigorous validation studies, because the vast majority of markers that look favorable turn out not to be reproducible,” said Prof. Leiserowitz; “We don’t want to raise people’s hopes only to find we don’t have a valid marker.”

Using mass spectrometry the researchers studied glycans in healthy women (n=100) and women with either early (n=52) or late (n=147) stage EOC. The first test, the “training set,” measured glycan expression in the serum samples and helped determine which glycans would help them differentiate between the groups. The candidate glycan-based biomarker panel developed with the training set distinguished women with EOC from healthy controls with 86% sensitivity, 95.8% specificity.

Then an independent “test set” was conducted, testing entirely new patient samples. These results showed detection of EOC with 70% sensitivity, 86% specificity, including both early and late stage EOC. The glycan candidate markers distinguished between healthy and early-stage EOC as accurately as the current standard diagnostic blood test CA-125.

Because sample selection can bias results, they then swapped samples, creating a new training set with the patients from the previous testing set, and vice versa. The results showed that the method works well, and that the developed markers are robust enough to be not overly influenced by patient selection. So although such tests tend to vary in their results depending on which patients are tested, in testing on different patient sample sets, these glycan markers continued to show promise as a diagnostic test for EOC.

“We take all these rigorous step-wise approaches to eliminate the possibility of bias,” said Prof. Leiserowitz. “This paper establishes that these are consistent and reproducible findings. This is a real phenomenon.” Nevertheless, the mechanisms behind the glycan changes are not understood—while the changes could be caused by cancer, they might also represent the body’s reaction to cancer—an inflammatory response, for example. The researchers caution that additional study and validation is needed before the markers are ready for clinical use.

Related Links:
UC Davis Comprehensive Cancer Center