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.
背景/目的：结肠癌、卵巢癌和前列腺癌的筛查与诊断面临侵入性操作和缺乏有效筛查手段的挑战。为应对这些挑战，我们开发了一种基于外泌体的液体活检检测方法，该方法采用新型外泌体生物标志物——α-连接的Thomsen–Friedenreich糖抗原（TF-Ag-α, Galβ1-3GalNAc-α）。该检测方法为结肠癌、卵巢癌和前列腺癌的筛查与诊断提供了一种具有高灵敏度和特异性的微创检测手段。 方法：采用专为临床转化设计的紧凑型表面等离子体共振生物传感器，检测10 μL血清样本中的外泌体TF-Ag-α水平。首先在由正常对照（n=80）和癌症患者（n=120，其中前列腺癌、结肠癌、卵巢癌各40例）组成的训练集中评估外泌体TF-Ag-α的诊断效能，随后在包含正常对照（n=29）和癌症患者（n=60，各癌种20例）的独立测试集中进行验证。通过受试者工作特征（ROC）曲线分析评估外泌体TF-Ag-α的诊断灵敏度、特异性及曲线下面积（AUC）。 结果：与正常对照组相比，癌症患者血清样本中的外泌体TF-Ag-α水平显著升高。当截断值为0.406时，外泌体TF-Ag-α区分所有癌症患者与正常对照的灵敏度达99.2%，特异性为100%，总体准确率为99.5%。 结论：这些发现证明了外泌体TF-Ag-α作为液体活检生物标志物在结肠癌、卵巢癌和前列腺癌检测中的临床转化潜力。
肿瘤(癌症)患者之家