Metabolic Profile May ID Early Ovarian Cancer

A metabolomic profile may hold the key for screening for early-stage ovarian cancer, according to a study published Nov. 17 in Scientific Reports. Researchers identified a profile of 16 blood-based diagnostic metabolites that could distinguish early-stage ovarian cancer patients with 100 percent accuracy. The researchers say these markers may yield a "clinically significant" diagnostic test with further validation.

Ovarian cancer is notoriously difficult to diagnose early, often leading to unsuccessful treatment. Given the low prevalence of the disease in the general population (0.1 percent in the United States), a screening test must attain "stringent accuracy," which the authors define as a positive predictive value of at least 10 percent, a specificity of more than 99 percent and a sensitivity of 75 percent or higher to be of clinical relevance in the general population. Current screening methods (trans-vaginal ultrasound combined with serum CA-125 levels) achieve a positive predictive value of only 24 percent.

"People have been looking at proteins for diagnosis of ovarian cancer for a couple of decades, and the results have not been very impressive," said co-author Facundo Fernández, Ph.D., from Georgia Institute of Technology, in a statement. "We decided to look in a different place for molecules that could potentially provide diagnostic capabilities. It's one of the places that people had really not studied before."

In the current study, the researchers evaluated serum samples from 46 early stage (I/II) serous epithelial ovarian cancer patients and 49 age-matched normal healthy controls. The samples were analyzed using ultra-performance liquid chromatography, high-resolution mass spectrometry (UPLC-MS) and tandem MS (MS/MS). This technology separates heavier molecules from lighter molecules to determine the molecular signatures.

One thousand candidate compounds were leaned to 255 by removing duplicates and unrelated molecules. These 255 were then analyzed by a learning algorithm, which evaluated the predictive value of each one. Molecules not contributing to the predictive accuracy of the screening were eliminated. Ultimately, the researchers identified 16 diagnostic metabolites that together are able to distinguish early-stage ovarian cancer with 100 percent accuracy.

"Molecular features closely associated with the cancer phenotype, like metabolites, may be expected to be less variable across patients than the broader spectrum of individual mutations and disrupted pathways underlying the disease," the researchers write in the paper.

Takeaway: Metabolomic profiles in serum may be useful in screening women for early- stage ovarian cancer. While further validation in larger populations is necessary, the researchers say a clinical assay based on the 16 markers is technically feasible.