Abstract 1919: Development of a diagnostic method for early-stage pancreatic cancer through exosome-derived microRNA profiling

Abstract [Background] Pancreatic cancer has an extremely poor prognosis, making early detection and treatment crucial. We have previously identified pancreatic cancer-specific exosomal microRNAs (Ex-miRs) from pancreatic juice in close contact with pancreatic cancer (Patent pending: PCT/JP2021/026597). [Purpose] To compare the diagnostic capability of pancreatic cancer-specific Ex-miRs in pancreatic juice and serum with existing tumor markers, and to evaluate their potential as non-invasive early diagnostic tools by investigating their detectability in stool samples. [Methods] We initially performed miRNA array analysis using pancreatic juice-derived Ex-miRs and identified pancreatic cancer-specific Ex-miRs through our proprietary methodology. qPCR was conducted using pancreatic juice from 15 pancreatic cancer patients (Stage 0/I/II/III/IV: 0/0/6/3/6) and 11 chronic pancreatitis patients. Subsequently, we analyzed serum samples from 4 pancreatic cancer patients and 5 chronic pancreatitis patients who provided both pancreatic juice and serum. We compared Ex-miR expression levels before and after curative resection in two Stage II cases and performed in situ hybridization (ISH) on one resected specimen. Further qPCR analysis was conducted on serum samples from 75 cases, including 40 pancreatic cancer patients (Stage 0/I/II/III/IV: 0/6/8/4/22) and patients with other gastrointestinal cancers. Finally, we analyzed Ex-miR expression in stool samples. [Results] We identified novel pancreatic cancer-specific Ex-miR-4516 and Ex-miR-4674 in pancreatic juice. In pancreatic juice diagnosis, Ex-miR-4516 and Ex-miR-4674 showed sensitivity, specificity, and accuracy of 80% and 73.3%, 81.8% and 90.9%, and 80.8% and 80.8%, respectively. Combining these Ex-miRs with cytology improved diagnostic accuracy (sensitivity/specificity/accuracy: 93.3/81.8/88.5%). In serum diagnosis, Ex-miR-4516 demonstrated high sensitivity (97.5%) for pancreatic cancer detection, with positive results in all six Stage 0/I cases. Ex-miR-4516 expression significantly decreased after curative resection in two Stage II cases (p<0.001). ISH analysis revealed high expression of miR-4516 and miR-4674 exclusively in pancreatic cancer cells. Stool analysis confirmed the feasibility of Ex-miR-4516 extraction and quantitative measurement, showing varying expression levels across samples. [Conclusions] These two pancreatic cancer-specific Ex-miRs were quantifiable in serum from early-stage pancreatic cancer patients. Serum Ex-miR-4516 showed promise for treatment response assessment and disease monitoring. Furthermore, Ex-miR-4516's detectability in stool suggests potential clinical application as a non-invasive early diagnostic tool for pancreatic cancer. Citation Format: Takahiko Sakaue, Hironori Koga, Hideki Iwamoto, Toru Nakamura, Atsutaka Masuda, Toshimitsu Tanaka, Hiroyuki Suzuki, Yohei Hara, Kyoyoshi Saito, Yutaka Shimamatsu, Sohei Yoshimura, Shingo Hirai, Hiroya Terabe, Hidetoshi Takedatsu, Takumi Kawaguchi. Development of a diagnostic method for early-stage pancreatic cancer through exosome-derived microRNA profiling [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 1919.