Detection of O-glycosylated CA125 by using an electrochemical immunosensor for ovarian cancer diagnosis

Abstract: Patients with ovarian cancer exhibit no clear symptoms. Ovarian cancer can be detected early only through internal diagnosis, ultrasound, and a carcinoma antigen 125 (CA125) tumor index test. More than 60% of patients have advanced ovarian cancer at diagnosis. The traditional chemical fluorescence immunoassay is used to measure CA125 levels; its lowest detection limit is only 35 U mL⁻¹, but it does not adequately demonstrate early symptoms. Moreover, endometriosis, pelvic cavity inflammation, and other gynecological diseases may increase CA125 levels. Therefore, a method for extracting CA125 information is urgently required for ovarian cancer diagnosis. This information can include the glycosylated state of CA125. In this study, a new ultrasensitive electrochemical immunosensor composed of reduced graphene oxide (rGO), gold nanoparticles, thionine chloride, bovine serum albumin, and two antibodies was developed. Through hydrogen peroxide reduction, the sensor can detect glycosylated CA125 from ovarian cancer cells and human blood serum by using differential pulse voltammetry. O₂ reacts with H⁺ that the H⁺ is formed from altered glycan core structures, producing a strong signal for malignancy detection. With the lowest detection limit of 4.10 pg mL⁻¹ (127 nU mL⁻¹), the sensor can be used for early ovary cancer detection. Furthermore, the results of a clinical test in healthy individuals and patients demonstrated the high selectivity of the immunosensor, and the high-regression-curve rate obtained from human blood serum analysis could be used to distinguish ovarian cancer from other gynecological diseases. This is the first study employing an electrochemical immunosensor to define and identify ovarian cancer to achieve highly specific and accurate detection. Graphic abstract: [Figure not available: see fulltext.].