Protein Patterns Investigated for Markers of Early Ovarian Cancer

The combination of liquid chromatography and tandem mass spectrometry enabled the discovery of four biomarkers holding promise to become “useful” in the development of a multipanel test for the early detection of ovarian cancer, according to a study published July 6 in BMC Cancer.

Diagnostic methods are notoriously lacking for early detection of ovarian cancer, with single cancer biomarkers, including cancer antigen 125 (CA125) and human epididymis protein 4 (HE4), having proven insufficient to detect early tumors. While two multimarker tests have been U.S. Food and Drug Administration-approved for evaluation of pelvic masses (Fujirebio Diagnostics’s ROMA test and Vermillion’s OVA1), no such tests exist for screening.

Identification of distinctive protein expression patterns is being held out as a promising strategy for understanding molecular alterations associated with ovarian cancer. In the BMC Cancer study serum samples (44 ovarian cancer and 45 healthy controls based on histopathological analysis) were pretreated using micropipette tips ZipTips, a solid-phase extraction method, was used as a depletion method with the goal of enabling low-molecular protein-peptide profiles. Using the combination of ZipTips technology and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) analysis generated a total of 170 spectral components (m/z unique peaks), with 98 peaks significantly different between the two groups.

Next, a classification model identified the most discriminative factors using three mathematical algorithms (SNN, GA, and QC). Finally, the results were verified on an independent test set of samples of (11 ovarian cancer patients and 12 healthy controls). The SNN model yielded the best differentiating capabilities and satisfactory values of sensitivity (71.0 percent) and specificity (68.6 percent).

“The novel approach, which enabled protein-peptide profiling as well as identification of four potential ovarian cancer biomarkers (complement C3, kininogen-1, inter-alpha-trypsin inhibitor heavy chain H4 and transthyretin) using MALDI-TOF MS, may contribute to the creation of new effective multicomponent diagnostic tools,” write the authors led by Agata Swiatly, from Poznan University of Medical Sciences in Poland.