The hunt is on to find biomarkers that detect cancer, but it's a challenging process. Early successes often are followed by heartbreaking failures. But now, researchers at UC Davis have verified that glycans (sugars attached to proteins) can be used to detect ovarian cancer. The study was published online in the journal Cancer Epidemiology, Biomarkers & Prevention.
"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 senior author Gary Leiserowitz, chief of the Division of Gynecologic Oncology. "So far, the results have been consistent and promising."
Creating a diagnostic tool that identifies ovarian cancer early through analysis of a blood sample would be an enormous benefit. Because the disease produces indistinct symptoms, such as bloating, ovarian cancer is often diagnosed late, making it difficult to treat.
The answer may be glycans, which are attached to over 50 percent of all proteins and often are altered when patients have cancer. By measuring these changes, the UC Davis team hopes to create a blood test that will find these cancers early.
Building on their previous work, the team conducted a series of experiments to ensure their glycan measurements were indeed detecting cancer. While they wanted to succeed, they also wanted to find any flaws in their method.
"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 Leiserowitz. "We don't want to raise people's hopes, only to find we don't have a valid marker."
Using mass spectrometry, which precisely analyzes molecules and determines their structures, the researchers studied glycans in healthy women and women with either early or advanced stage ovarian cancer.
The first test, called a "training set," measured different glycan expression in the serum samples and helped determine which sugars would help them differentiate between patient groups. The glycan-based biomarker panel developed with the training set distinguished women with ovarian cancer from healthy controls with 86 percent accuracy.
The researchers then conducted a "test set," applying those measurements to entirely new patient samples. This also produced excellent results, detecting cancer with 70 percent accuracy, including both early- and late-stage cancers. The glycan markers distinguished between healthy and early-stage cancers as well as the standard diagnostic blood test for ovarian cancer, 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.
Researchers caution that additional study is needed before the markers are ready for clinical use because they don't fully understand the mechanisms behind the glycan changes. While the changes could be caused by cancer, they might also represent the body's reaction to cancer -- an inflammatory response, for example.
Results of these tests can vary depending on which patients are tested. However, despite testing on different patient sample sets, the glycan markers continued to show promise as a diagnostic test for ovarian cancer.
"We take all these rigorous step-wise approaches to eliminate the possibility of bias," Leiserowitz said. "This paper establishes that these are consistent and reproducible findings. This is a real phenomenon."
- K. Kim, L. R. Ruhaak, U. T. Nguyen, S. L. Taylor, L. Dimapasoc, C. Williams, C. Stroble, S. Ozcan, S. Miyamoto, C. B. Lebrilla, G. S. Leiserowitz. Evaluation of Glycomic Profiling as a Diagnostic Biomarker for Epithelial Ovarian Cancer. Cancer Epidemiology Biomarkers & Prevention, 2014; DOI: 10.1158/1055-9965.EPI-13-1073
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