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Figure S3 from Exosomal Thomsen–Friedenreich Glycoantigen: A New Liquid Biopsy Biomarker for Lung and Breast Cancer Diagnoses

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posted on 2024-10-01, 14:00 authored by Chang-Chieh Hsu, Yafei Su, Kate Rittenhouse-Olson, Kristopher M. Attwood, Wilfrido Mojica, Mary E. Reid, Grace K. Dy, Yun Wu

Supplementary Figure S3. Sensing performance of SPR assay in detecting exosomal TF-Ag-α. Exosomes from A549 NSCLC cells (a) and MDA-MB-231 breast cancer cells (b) were spiked in the serum of a normal control at concentrations of 0 to 10^11 exosomes/mL. The expression of exosomal TF-Ag-α was measured using the SPR assay. For A549 cell-derived exosomes, the LOD was 5×10^9 exosomes/mL and the linear range was from 5×10^9 to 10^11 exosomes/mL. For MDA-MB-231 cell-derived exosomes, the LOD was 10^9 exosomes/mL and the linear range was from 10^9 to 10^11 exosomes/mL.

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ARTICLE ABSTRACT

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 biomolecule, have not yet been explored for this purpose. In this study, we reported a new exosomal carbohydrate biomarker, α-linked Thomsen–Friedenreich glycoantigen (TF-Ag-α; Galβ1-3GalNAc-α). To translate our discovery into clinical settings, we developed a surface plasmon resonance–based assay which utilized a unique mAb, JAA-F11, with high specificity to measure the levels of exosomal TF-Ag-α in blood. To the best of 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 patients with cancer, but in contrast, levels were negligible in those from normal controls. With a total of 233 patients with cancer 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. Exosomes or small extracellular vesicles have emerged as potent biomarkers of cancer liquid biopsy. We discovered a new exosomal carbohydrate marker, TF-Ag-α (Galβ1-3GalNAc-α), and showed that exosomal TF-Ag-α detected both lung and breast cancers with >95% accuracy. Our findings demonstrated that exosomal TF-Ag-α is a promising liquid biopsy biomarker for cancer screening and early detection.

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