InterVenn Biosciences, South San Francisco, CA, USA.
Division of Gynecologic Oncology, University of Cincinnati Cancer Center, Cincinnati, OH, USA.
Br J Cancer. 2024 Jun;130(10):1716-1724. doi: 10.1038/s41416-024-02644-4. Epub 2024 Apr 24.
There is a need for diagnostic tests for screening, triaging and staging of epithelial ovarian cancer (EOC). Glycoproteomics of blood samples has shown promise for biomarker discovery.
We applied glycoproteomics to serum of people with EOC or benign pelvic masses and healthy controls. A total of 653 analytes were quantified and assessed in multivariable models, which were tested in an independent cohort. Additionally, we analyzed glycosylation patterns in serum markers and in tissues.
We identified a biomarker panel that distinguished benign lesions from EOC with sensitivity and specificity of 83.5% and 90.1% in the training set, and of 86.7 and 86.7% in the test set, respectively. ROC analysis demonstrated strong performance across a range of cutoffs. Fucosylated multi-antennary glycopeptide markers were higher in late-stage than in early-stage EOC. A comparable pattern was found in late-stage EOC tissues.
Blood glycopeptide biomarkers have the potential to distinguish benign from malignant pelvic masses, and early- from late-stage EOC. Glycosylation of circulating and tumor tissue proteins may be related. This study supports the hypothesis that blood glycoproteomic profiling can be used for EOC diagnosis and staging and it warrants further clinical evaluation.
需要用于筛查、分诊和分期上皮性卵巢癌(EOC)的诊断测试。血液样本的糖蛋白质组学在发现生物标志物方面显示出了前景。
我们将糖蛋白质组学应用于患有 EOC 或良性盆腔肿块以及健康对照者的血清中。对 653 种分析物进行了定量分析,并在多变量模型中进行了评估,然后在独立队列中进行了测试。此外,我们还分析了血清标志物和组织中的糖基化模式。
我们确定了一个可以将良性病变与 EOC 区分开的生物标志物组,在训练组中的敏感性和特异性分别为 83.5%和 90.1%,在测试组中的敏感性和特异性分别为 86.7%和 86.7%。ROC 分析证明了在一系列截止值下的优异性能。晚期 EOC 中的岩藻糖基化多天线糖肽标志物高于早期 EOC。晚期 EOC 组织中也发现了类似的模式。
血液糖肽生物标志物具有区分良性和恶性盆腔肿块以及早期和晚期 EOC 的潜力。循环和肿瘤组织蛋白的糖基化可能有关。这项研究支持了血液糖蛋白质组分析可用于 EOC 诊断和分期的假说,并需要进一步的临床评估。