Liquid biopsy for early detection of pancreatic ductal adenocarcinoma

IF 52.5 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Nature Medicine Pub Date : 2026-09-16 DOI:10.1038/s41591-026-04625-x

Caiming Xu, Alessandro Mannucci, Haiyong Han, Ruben M. Munoz, Derek Cridebring, Sourat Darabi, Yuji Toiyama, Yoshinaga Okugawa, Gagandeep Singh, Mustafa Raoof, Joon Oh Park, James Lin, Gregory Idos, Michael J. Demeure, Erkut Borazanci, Douglas B. Evans, Susan Tsai, Eunsung Jun, Carlos Becerra, Scott A. Celinski, Laleh Melstrom, Vincent Chung, Guixin Zhang, Dong Shang, David L. Bartlett, Mitsuro Kanda, Song Cheol Kim, Valsamo Anagnastou, Giulia Martina Cavestro, John S. Bolton, Ali H. Zaidi, Daniel Von Hoff, Ajay Goel

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Abstract

There is no clinically relevant blood-based assay for the detection of early-stage pancreatic ductal adenocarcinoma (PDAC), a solid malignancy characterized by poor outcomes. Here we developed, validated and tested a blood-based microRNA (miRNA) assay (which included hsa-miR-142-3p, hsa-miR-30c-5p, hsa-miR-335-5p, hsa-miR-340-5p, hsa-miR-200b-3p, hsa-miR-1260b, hsa-miR-145-3p, hsa-miR-145-5p, hsa-miR-429 and hsa-miR-200a-3p) and a composite score, PANXEON (PANcreatic cancer eXosome Early detectiON), that integrates the miRNA signature with carbohydrate antigen 19-9 for the detection of early-stage PDAC. We conducted an international, multicenter, observational, prospective biomarker study that involved 1,785 individuals with and without PDAC from four countries. The miRNA signature achieved an area under the receiver operating characteristic curve of 88.6% in the testing cohort, with a sensitivity of 83.8% for early-stage PDAC, while showing minimal cross-reactivity with other gastrointestinal cancers. In a cohort of 19 individuals, the miRNA signature levels decreased during neoadjuvant chemotherapy and after surgery and increased before disease recurrence. When combined with carbohydrate antigen 19-9 levels, this blood assay demonstrated a sensitivity of 86.8% for stage I–II PDAC, false-positive rates of 3.2% in low-risk controls and 15.6% in high-risk controls in the testing cohort. PANXEON demonstrates potential for detecting high-grade dysplasia in individuals with high-risk pancreatic cysts (64.3%). Collectively, we present a composite biomarker that may complement existing strategies for the detection of early-stage PDAC and warrants further large-scale prospective studies. ClinicalTrials.gov registration: NCT06388967 . In a prospective study involving 1,785 individuals from four countries, the PANXEON exosome-based biomarker, combined with carbohydrate antigen 19-9 levels, achieves high sensitivity for the detection of early-stage pancreatic cancer.

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液体活检在胰腺导管腺癌早期诊断中的应用。

早期胰腺导管腺癌（PDAC）是一种预后较差的实体恶性肿瘤，目前尚无临床相关的基于血液的检测方法。在这里，我们开发、验证和测试了一种基于血液的miRNA （miRNA）测定方法（包括hsa-miR-142-3p、hsa-miR-30c-5p、hsa-miR-335-5p、hsa-miR-340-5p、hsa-miR-200b-3p、hsa-miR-1260b、hsa-miR-145-3p、hsa-miR-145-5p、hsa-miR-429和hsa-miR-200a-3p）和一种综合评分PANXEON（胰腺癌外泌体早期检测），该方法将miRNA特征与碳水化合物抗原19-9结合起来，用于检测早期PDAC。我们进行了一项国际、多中心、观察性、前瞻性生物标志物研究，涉及来自四个国家的1785名PDAC患者和非PDAC患者。在测试队列中，miRNA标记在接受者工作特征曲线下的面积为88.6%，对早期PDAC的敏感性为83.8%，而与其他胃肠道癌症的交叉反应性最小。在19个个体的队列中，miRNA标记水平在新辅助化疗期间和手术后下降，在疾病复发前上升。当与碳水化合物抗原19-9水平结合时，该血液检测显示I-II期PDAC的敏感性为86.8%，低风险对照组的假阳性率为3.2%，高风险对照组的假阳性率为15.6%。PANXEON显示出在高风险胰腺囊肿患者中检测高级别发育不良的潜力（64.3%）。总之，我们提出了一种复合生物标志物，可以补充现有的早期PDAC检测策略，并值得进一步大规模的前瞻性研究。ClinicalTrials.gov注册：NCT06388967。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Nature Medicine 医学-生化与分子生物学

CiteScore

100.90

自引率

0.70%

发文量

525

审稿时长

1 months

期刊介绍： Nature Medicine is a monthly journal publishing original peer-reviewed research in all areas of medicine. The publication focuses on originality, timeliness, interdisciplinary interest, and the impact on improving human health. In addition to research articles, Nature Medicine also publishes commissioned content such as News, Reviews, and Perspectives. This content aims to provide context for the latest advances in translational and clinical research, reaching a wide audience of M.D. and Ph.D. readers. All editorial decisions for the journal are made by a team of full-time professional editors. Nature Medicine consider all types of clinical research, including: -Case-reports and small case series -Clinical trials, whether phase 1, 2, 3 or 4 -Observational studies -Meta-analyses -Biomarker studies -Public and global health studies Nature Medicine is also committed to facilitating communication between translational and clinical researchers. As such, we consider “hybrid” studies with preclinical and translational findings reported alongside data from clinical studies.