Abstract:
Ovarian cancer (OC) results in some 150,000 deaths worldwide of nearly 300,000 new cases each year. Unfortunately, only 20 % of patients are diagnosed at the early stages (I and II) of the disease when treatment is most effective, leading to a 5- year relative survival rate of only 20 %. Early diagnosis of OC improves survival rate to 93 %; however, there is a lack of early diagnose due to few specific symptoms being observed, and the absence of reliable, cost-effective mass screening techniques. Several biomarkers have been identified for OC, of which cancer antigen-125 (CA125) is the only one currently clinically approved. However, the use of the CA125’assay is limited to high-risk women, and it is often performed with a transvaginal ultrasound. Although CA125 is elevated in over 90 % of late-stage OC cases, it is elevated in only 50 % of early-stage cases and can yield false-positive and false-negative results A highly attractive possibility with regard to biomarker detection would be the incorporation of a biosensor into the conventional automated robotic system to process and test patient samples. Such a technology would require device reversible signalling or flow-through cleaning, appropriate sensitivity and, critically, the capability of operation in a biological fluid. The reality is that the issue of fouling by components of such fluids has constituted a major problem.
Lysophosphatidic acid (LPA) is a distinctly attractive potential biomarker for OC with high sensitivity (98 %) and specificity. The normal level of LPA in the body is 0–5 μM, but increases to 5–50 μM in OC, even in stage I. In our research, we are employing three different biosensor-based strategies for LPA detection in tandem with that for CA-125. These techniques include an ultra-high frequency acoustic wave device, a chemiluminescence-based iron oxide nanoparticle (IONP) approach and electrochemical detection based on both square wave and differential pulse voltammetry. For assay of LPA all these methods incorporate the protein complex gelsolin-actin, which enables testing for detection of the biomarker binding to the complex results in separation of gelsolin from actin. In proof of concept experiments, each of the approaches is capable of the detection of LPA at the sub micromole level. In addition to the work with LPA we are developing an electrochemical system for the tandem assay of CA-125 which is based on an aptamer probe for the marker.
