Abstract A076: Comparison of Urinary and Plasma Extracellular Small Noncoding RNA Profiles for Pancreatic Cancer Detection in a High-Risk Population
Nicholas J. Bevins, Satomura Atsushi, Yuki IchikawaAbstract
Background:
Pancreatic ductal adenocarcinoma (PDAC) remains one of the deadliest cancers because it is rarely detected at a curable stage. Current surveillance of high-risk (HR) individuals relies on imaging and clinical risk factors with limited sensitivity for early disease. Urinary extracellular small noncoding RNAs (sncRNAs), including microRNAs (miRNAs), represent a promising non-invasive biomarker. Craif’s urine-based extracellular sncRNA platform has been commercially available in Japan as a multi-cancer early detection test since 2023 (>80,000 tests). To support U.S. commercialization, a Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory is being established in San Diego, California and U.S. studies are underway to validate the platform for detection of high-grade dysplasia (HGD) and PDAC.
Methods:
Urine and plasma were collected from 18 patients with PDAC and 28 HR individuals (type 2 diabetes, n=14; pancreatic cysts, n=10; chronic pancreatitis, n=4). Extracellular sncRNAs, including miRNAs, PIWI-interacting RNAs (piRNAs), and transfer RNA derived fragments (tRFs), were profiled by next-generation sequencing using methods transferred from Japan.
Results:
All samples yielded sufficient sncRNA for analysis. Plasma samples contained 23,919-739,682 unique molecules comprised of 1,918 unique sncRNA species (722 miRNAs, 1,059 piRNAs, and 137 tRFs). Urine samples contained 9,937-5,080,485 unique molecules comprised of 5,646 unique sncRNA species (1,345 miRNAs, 4,055 piRNAs, and 246 tRFs). Plasma showed minimal differences between PDAC and HR individuals, with no differentially expressed miRNAs or tRFs and only two upregulated piRNAs. In contrast, urine identified 13 upregulated and 4 downregulated miRNAs, 41 upregulated and 1 downregulated piRNAs, and no differentially expressed tRFs (false discovery rate <0.1; |log2 fold change| >1). Similar differential expression patterns were previously observed in Japanese cohorts. Pathway analysis of differentially expressed miRNAs suggested a T-cell origin.
Conclusions:
Craif’s extracellular sncRNA sequencing platform was successfully implemented in the United States using methods transferred from Japan. Compared with plasma, urine yielded a more diverse extracellular sncRNA profile and demonstrated substantially greater differential expression between PDAC and HR individuals. Concordant urinary signatures across U.S. and Japanese cohorts support cross-population reproducibility, while enrichment of immune-derived transcripts suggests urine captures disease-associated signals not readily detected in plasma. These findings support further evaluation of urine-derived sncRNAs as non-invasive biomarkers for early detection of HGD and PDAC in larger U.S. studies.
Citation Format:
Nicholas J. Bevins, Satomura Atsushi, Yuki Ichikawa. Comparison of Urinary and Plasma Extracellular Small Noncoding RNA Profiles for Pancreatic Cancer Detection in a High-Risk Population [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A076.