Department of Biomedical Engineering, University at Buffalo, The State University of New York, Buffalo, New York.
For-Robin, Inc., Buffalo, New York.
Cancer Res Commun. 2024 Aug 1;4(8):1933-1945. doi: 10.1158/2767-9764.CRC-23-0505.
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.
外泌体是细胞释放的纳米级细胞外囊泡，用于在细胞间传递生物分子，如蛋白质和 RNA。外泌体在癌症的发生和转移中起着重要作用；因此，它们已成为癌症筛查、诊断和治疗的潜在液体活检生物标志物。许多外泌体 cargo，包括蛋白质、RNA 和脂质，已被广泛研究作为癌症液体活检的生物标志物。然而，糖类作为一种重要的生物分子，尚未被探索用于此目的。在这项研究中，我们报告了一种新的外泌体糖生物标志物，α-连接的 Thomason-Friedenreich 糖抗原（TF-Ag-α；Galβ1-3GalNAc-α）。为了将我们的发现转化为临床环境，我们开发了一种基于表面等离子体共振的测定方法，该方法利用一种独特的 mAb，JAA-F11，具有高特异性来测量血液中外泌体 TF-Ag-α 的水平。据我们所知，我们是第一个证明外泌体携带 TF-Ag-α 的人。我们在癌症患者的低至 10 μL 血清样本中检测到外泌体 TF-Ag-α，但相比之下，正常对照组的水平可以忽略不计。在总共 233 名癌症患者和正常对照组中，我们表明外泌体 TF-Ag-α可以检测肺癌（n=60）和乳腺癌（n=95）与正常对照组（n=78）的准确率分别≥95%和≥97%。这些结果表明，外泌体 TF-Ag-α 是癌症诊断的潜在液体活检生物标志物。
外泌体或小细胞外囊泡已成为癌症液体活检的有效生物标志物。我们发现了一种新的外泌体糖标记物 TF-Ag-α（Galβ1-3GalNAc-α），并表明外泌体 TF-Ag-α 的检测准确率>95%。我们的研究结果表明，外泌体 TF-Ag-α 是癌症筛查和早期检测的有前途的液体活检生物标志物。
