Screening and longitudinal analysis of different circulatory glycoproteins in the monitoring of lung cancer

Abstract

Lung cancer (LC) is the second most prevalent cancer, and it has the highest mortality rate of all cancers globally in both genders. There are several treatment options for LC, but patients often develop resistance to treatment, thus their status needs to be monitored throughout. However, there is currently no biomarker in clinical use for treatment monitoring of LC patients; the monitoring only relies on imaging techniques. Glycosylation changes are considered a hallmark of cancer and recognizing these changes could lead to a specific and sensitive biomarker development. This could be achieved with lectins, carbohydrate-binding proteins with high specificity but these molecules have poor affinity towards the sugar moieties. The issue with low affinities can be remedied by coating them on fluorescent europium chelate-doped-nanoparticles (NPs), which increases avidity, resulting in sensitive and specific detection of glycosylation changes. The aim of this project was to find sensitive and specific novel glycovariant-assays based on lectin-NP for assessment of treatment response in LC patient by detection of LC associated glycovariants (GVs). Combinations of immobilized capture antibodies binding four different circulatory glycoproteins (CA125, CA19-9, CEA and CA15-3) and of four lectin-NPs (UEA, MBL, WGA, WFL) conjugated as tracers targeting specific glycan structures (fucose, mannose, N-acetylglucosamine and N-acetylgalactosamin) were used. Combinations were assayed and optimized in progressive EDTA-plasma samples of seven LC patients. The preliminary results obtained during this research show promise for one CA19-9 and one CA125 GV as potential biomarkers that reflect patients’ response to treatment. These GVs could alert clinicians much faster about drug responses in individuals, improving their treatment.