Moore Travis W, Spiliotopoulos Elias, Callahan Rowan L, Kirschbaum C Ward, Bailey Conner F, Kim Hyun Ji, Roskams-Hieter Breeshey, Goncalves Florian, Keith Dove, Grossberg Aaron J, Spellman Paul T, Mills Gordon B, Sears Rosalie C, Morgan Terry K, Ngo Thuy T M
Cancer Early Detection Advanced Research Center (CEDAR), Knight Cancer Institute, Oregon Health and Science University, Portland, OR, USA.
Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR, USA.
Nat Commun. 2025 Aug 9;16(1):7345. doi: 10.1038/s41467-025-62685-y.
Pancreatic ductal adenocarcinomas (PDAC) are among the most fatal cancers, in part due to frequent detection at advanced stages. Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), the most sensitive diagnostic method of PDAC in current standard clinical practice, is invasive, costly, with access limited to major healthcare settings. Here, we present a non-invasive evaluation of plasma cell-free RNA (cfRNA) for PDAC detection in pre-diagnostic high-risk and de novo symptomatic patients presenting for EUS-FNA. We develop a cfRNA normalization method to account for preanalytical variation and handling effects and derive 29 potential cfRNA biomarkers for PDAC diagnosis using 153 samples collected prior to the EUS procedure. Biomarkers related to liver function are elevated in PDAC samples, including early-stage patients without liver metastasis. Classification of PDAC using these biomarkers is validated using an independent cohort of 95 samples. Our findings could help to improve diagnostic utility in high-risk and symptomatic individuals.
胰腺导管腺癌（PDAC）是最致命的癌症之一，部分原因是常在晚期才被发现。内镜超声引导下细针穿刺活检（EUS-FNA）是当前标准临床实践中检测PDAC最敏感的诊断方法，但具有侵入性、成本高，且仅适用于大型医疗机构。在此，我们对接受EUS-FNA检查的诊断前高危和初发症状患者的血浆游离RNA（cfRNA）进行无创评估以检测PDAC。我们开发了一种cfRNA标准化方法，以考虑分析前的变异和处理影响，并使用EUS检查前收集的153份样本得出29种潜在的用于PDAC诊断的cfRNA生物标志物。与肝功能相关的生物标志物在PDAC样本中升高，包括无肝转移的早期患者。使用95份样本的独立队列验证了使用这些生物标志物对PDAC的分类。我们的研究结果可能有助于提高高危和有症状个体的诊断效用。
