Exosomal Thomsen-Friedenreich Glycoantigen: A New Liquid Biopsy Biomarker for Lung and Breast Cancer Diagnosis.

Exosomes are nanosized extracellular vesicles released by cells to transport biomolecules such as proteins and RNAs for intercellular communication. Exosomes play important roles in cancer development and metastasis; therefore, they have emerged as potential liquid biopsy biomarkers for cancer screening, diagnosis and management. Many exosome cargos, including proteins, RNAs and lipids, have been extensively investigated as biomarkers for cancer liquid biopsy. However, carbohydrates, an important type of biomolecules, have not yet been explored for this purpose. In this study, we reported a new exosomal carbohydrate biomarker, i.e., alpha-linked Thomsen-Friedenreich glycoantigen (TF-Ag-α; Galβ1-3GalNAc alpha). To transform our discovery for clinical applications, we developed a surface plasmon resonance (SPR)-based assay which utilized a unique monoclonal antibody, JAA-F11, with high specificity to TF-Ag-α to measure the levels of exosomal TF-Ag-α in blood. To our knowledge, we are the first to demonstrate that exosomes carry TF-Ag-α. We detected exosomal TF-Ag-α in as low as 10 μL serum samples from cancer patients but in contrast, levels were negligible from normal controls. With a total of 233 cancer patients and normal controls, we showed that exosomal TF-Ag-α detected lung cancer (n=60) and breast cancer (n=95) from normal controls (n=78) with ≥95% and ≥97% accuracy, respectively. These results demonstrated that exosomal TF-Ag-α is a potential liquid biopsy biomarker for cancer diagnosis.