Pancreatic ductal adenocarcinoma (PDAC) is often diagnosed too late for effective therapy. The classic strategy for early detection biomarker advancement consists of initial retrospective phases of discovery and validation with tissue samples taken from individuals diagnosed with disease, compared to controls. Using this approach, we previously reported the discovery of a blood biomarker panel consisting of thrombospondin-2 (THBS2) and CA19-9 that together could discriminate resectable stage I and IIa PDAC as well as stages III and IV PDAC, with c-statistic values in the range of 0.96-0.97 in two Phase 2 studies. We now report that in two studies of blood samples prospectively collected from one to fifteen years prior to a PDAC diagnosis (Mayo Clinic and PLCO cohorts), THBS2 and/or CA19-9 failed to discriminate cases from healthy controls at the AUC=0.8 needed. We conclude that PDAC progression may be heterogeneous and for some individuals can be more rapid than generally appreciated. It is important that PDAC early detection studies incorporate high-risk, prospective pre-diagnostic cohorts into discovery and validation studies.

中文翻译：

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THBS2/CA19-9 在诊断时检测胰腺导管腺癌在诊断前检测中表现不佳：对生物标志物进步的影响

胰腺导管腺癌 (PDAC) 的诊断通常为时已晚，无法进行有效治疗。与对照组相比，早期检测生物标志物进步的经典策略包括发现和验证的初始回顾阶段，这些阶段取自被诊断患有疾病的个体的组织样本。使用这种方法，我们之前报道了由血小板反应蛋白 2 (THBS2) 和 CA19-9 组成的血液生物标志物组的发现，它们一起可以区分可切除的 I 期和 IIa 期 PDAC 以及 III 期和 IV 期 PDAC，具有 c 统计值在两项 2 期研究中的范围为 0.96-0.97。我们现在报告说，在 PDAC 诊断前一到十五年前瞻性收集的血液样本的两项研究中（梅奥诊所和 PLCO 队列），THBS2 和/或 CA19-9 未能在所需的 AUC=0.8 时将病例与健康对照区分开来。我们得出结论，PDAC 进展可能是异质的，并且对于某些人来说可能比普遍认为的更快。重要的是，PDAC 早期检测研究将高风险、前瞻性的诊断前队列纳入发现和验证研究。