Nanoparticle-based chemiluminescent detection of an ovarian cancer biomarker – A clinically-relevant pilot study

Biomarker based detection for ovarian cancer (OC) in clinical settings is currently focused on the biomarker CA-125. This marker unfortunately has a fairly low sensitivity and specificity for ovarian cancer at only 82% and 67% respectively.  It is also lacking in stage I ovarian cancer patients, when the disease is at its most treatable. A promising blood-based biomarker for ovarian cancer is lysophosphatidic acid (LPA), which is a cell-signaling lipid that has been shown to be elevated in patients with OC. In separate studies this signaling lipid was found to be elevated in 90% of stage I ovarian cancer patients, and 100% of later stage patients with concentrations between 1.3 and 50 μM relating to cancer. Before LPA can be employed in clinical studies, however, there is a requirement for a method of detection that is rapid, low-cost, sensitive, specific, and amenable to automation for high-throughput screening.

We have been able to develop multiple LPA sensors that utilize the natural relationship between gelsolin 1–3, actin, and LPA for specific detection of LPA. Gelsolin 1–3 encompasses the first three domains of gelsolin, an 82 kDa actin-binding protein that regulates cell motility and morphology by assembling and disassembling actin. Actin is a 42 kDa cell structural protein that forms microfilaments in the cytoskeleton. LPA regulates actin–gelsolin binding, causing the release of actin when it binds to the actin–gelsolin complex. We have previously taken advantage of this relationship to create LPA sensors based on fluorescence, electrochemistry, and acoustic wave technology.

More recently we have adapted this assay to work with chemiluminescent detection on a magnetic nanoparticles support.  This initial study found that our test was able to detect low levels of LPA in buffer solution. More recent, yet unpublished experiments have found a production method that drastically reduces the test to test error and also allows measurement of clinically relevant levels of LPA in simulated serum samples. This study aims to determine if our test can be used in a clinical application for the detection of ovarian cancer.  Our test does not aim to alter the standard of care, only to create a new tool for ovarian cancer diagnosis that can be added to the current toolkit available to doctors.

Professor Michael Thompson was appointed Lecturer in Instrumental Analysis at Loughborough University in 1971. He then moved to the University of Toronto where he is now Professor of Bioanalytical Chemistry. He is recognized internationally for his pioneering work over many years in the area of research into new biosensor technologies. His research is centered on the surface chemistry of proteins, cells and bacteria. Professor Michael has been awarded many prestigious international prizes for his research including the Robert Boyle Gold Medal of the Royal Society of Chemistry, the Elsevier Prize in Biosensor and Bioelectronics Technology, the E.W.R. Steacie Award of the Chemical Society of Canada, and recently the 2023 Royal Society of Chemistry Horizons Prize in Analytical Science.