Binkowski Braelyn, Klamer Zachary, Gao ChongFeng, Staal Ben, Repesh Anna, Tran Hoang-Le, Brass David M, Bartlett Pamela, Gallinger Steven, Blomqvist Maria, Morrow J Bradley, Allen Peter, Shi Chanjuan, Singhi Aatur, Brand Randall, Huang Ying, Hostetter Galen, Haab Brian B
Van Andel Institute, Grand Rapids, MI, USA.
Trinity Health, Grand Rapids, MI, USA.
Sci Adv. 2025 Mar 7;11(10):eadt0029. doi: 10.1126/sciadv.adt0029.
Pancreatic ductal adenocarcinoma (PDAC) tumor heterogeneity impedes the development of biomarker assays for early disease detection. We hypothesized that PDAC cell subpopulations could be identified by aberrant glycan signatures in both tumor tissue and blood samples. We used multiplexed glycan immunofluorescence to distinguish between PDAC and noncancer cell subpopulations within tumor tissue, and we developed hybrid glycan sandwich assays to determine whether the aberrant glycan signatures could be detected in blood samples. We found that PDAC cells were identified by signatures of glycans detected by four glycan-binding proteins (VVL, CA19-9, sTRA, and GM2) and that there are three types of glycan-defined PDAC tumors: sTRA type, CA19-9 type, and intermixed. In patient-matched tumor and blood samples, the PDAC tumor type could be determined by the aberrant glycans in the blood. As a result, the combined assays of aberrant glycan signatures were more sensitive and specific than any individual assay. Our results demonstrate a methodology to detect and stratify PDAC.
胰腺导管腺癌（PDAC）的肿瘤异质性阻碍了用于早期疾病检测的生物标志物检测方法的发展。我们假设，可以通过肿瘤组织和血液样本中的异常聚糖特征来识别PDAC细胞亚群。我们使用多重聚糖免疫荧光来区分肿瘤组织中的PDAC和非癌细胞亚群，并开发了混合聚糖夹心测定法，以确定是否可以在血液样本中检测到异常聚糖特征。我们发现，通过四种聚糖结合蛋白（VVL、CA19-9、sTRA和GM2）检测到的聚糖特征可以识别PDAC细胞，并且存在三种聚糖定义的PDAC肿瘤类型：sTRA型、CA19-9型和混合型。在患者匹配的肿瘤和血液样本中，可以通过血液中的异常聚糖来确定PDAC肿瘤类型。因此，异常聚糖特征的联合检测比任何单独的检测都更敏感、更特异。我们的结果证明了一种检测和分层PDAC的方法。
