Exosomal Thomsen-Friedenreich Glycoantigen as a Sensitive and Specific Biomarker for Colon, Ovarian and Prostate Cancer Diagnosis.

Background/Objectives: The screening and diagnosis of colon, ovarian, and prostate cancers are challenged by invasive procedures and lack of effective screening tests. To address these challenges, we developed an exosome-based liquid biopsy assay that utilized a new exosomal biomarker, α-linked Thomsen-Friedenreich glycoantigen (TF-Ag-α, Galβ1-3GalNAc-α). This assay provides a minimally invasive method with high sensitivity and specificity for the screening and diagnosis of colon, ovarian and prostate cancers. Methods: Exosomal TF-Ag-α levels in 10 μL serum samples were measured using a compact, surface plasmon resonance-based biosensor developed to facilitate clinical translation. The diagnostic performance of exosomal TF-Ag-α was initially evaluated in a training set consisting of normal controls (n = 80) and cancer patients (n = 120, 40 for prostate, 40 for colon, and 40 for ovarian cancer), and then validated in an independent test set including normal controls (n = 29) and cancer patients (n = 60, 20 for each cancer type). Receiver operating characteristic (ROC) analysis was performed to assess diagnostic sensitivity, specificity and area under the curve (AUC) of exosomal TF-Ag-α. Results: Serum samples from cancer patients showed significantly elevated levels of exosomal TF-Ag-α compared with normal controls. Exosomal TF-Ag-α distinguished all cancer patients from normal controls with a sensitivity of 99.2%, specificity of 100% and an overall accuracy of 99.5% at a cutoff value of 0.406. Conclusions: These findings demonstrated the clinical translational promise of exosomal TF-Ag-α as a liquid biopsy biomarker for the detection of colon, ovarian and prostate cancers.