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Pancreatic Juice-Derived microRNA-4516 and microRNA-4674 as Novel Biomarkers for Pancreatic Ductal Adenocarcinoma
Takahiko Sakaue1,2,3, Hironori Koga1,2, Hideki Iwamoto1,2
1Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
Background And Aims:
Precise diagnostic biomarkers are urgently required for pancreatic ductal adenocarcinoma (PDAC). Therefore, the aim of this study was to identify PDAC-specific exosomal microRNAs (Ex-miRs) from pancreatic juice (PJ) and evaluate their diagnostic potential.
Methods:
Exosomes in PJ and serum were extracted using ultracentrifugation and confirmed morphologically and biochemically. PDAC-specific Ex-miRs were identified using our original miR arrays, in which "Ex-miRs derived from the PJ of patients with chronic pancreatitis (CP)" were subtracted from Ex-miRs commonly expressed in both "human PDAC cell lines" and "the PJ of patients with PDAC." We verified the expression of these miRs using quantitative real-time reverse transcription polymerase chain reaction. Changes in serum Ex-miR levels were assessed in 2 patients with PDAC who underwent curative resection. In situ hybridization was performed to directly visualize PDAC-specific miR expression in cancer cells.
Results:
We identified novel Ex-miR-4516 and Ex-miR-4674 from the PJ of patients with PDAC, and they showed 80.0% and 81.8% sensitivity, 80.8% and 73.3% specificity, and 90.9% and 80.8% accuracy, respectively. The sensitivity, specificity, and accuracy of a triple assay of Ex-miR-4516/4674/PJ cytology increased to 93.3%, 81.8%, and 88.5%, respectively. In serum samples (n = 88), the sensitivity, specificity, and accuracy of Ex-miR-4516 were 97.5%, 34.3%, and 68%, respectively. Presurgical levels of serum-derived Ex-miR-4516 in 2 patients with relatively early disease stages declined after curative resection. In situ hybridization demonstrated that Ex-miR-4516 expression exclusively occurred in cancer cells.
Conclusion:
Liquid assays using the in situ-proven Ex-miR-4516 may have a high potential for detecting relatively early-stage PDAC and monitoring its clinical course.
Insights
Researchers identified two novel exosomal microRNAs (Ex-miRs), Ex-miR-4516 and Ex-miR-4674, in pancreatic juice for diagnosing pancreatic ductal adenocarcinoma (PDAC). These biomarkers show high potential for early detection and monitoring of PDAC.
Area of Science:
- Oncology
- Biomarker Discovery
- Molecular Diagnostics
Background:
- Pancreatic ductal adenocarcinoma (PDAC) lacks precise diagnostic biomarkers.
- Early detection of PDAC is crucial for improving patient outcomes.
Purpose of the Study:
- To identify PDAC-specific exosomal microRNAs (Ex-miRs) from pancreatic juice (PJ).
- To evaluate the diagnostic potential of identified Ex-miRs for PDAC.
Main Methods:
- Exosomes were extracted from PJ and serum via ultracentrifugation.
- PDAC-specific Ex-miRs were identified using miR arrays and validated with quantitative real-time PCR.
- In situ hybridization was used to visualize Ex-miR expression in cancer cells.
Main Results:
- Novel Ex-miR-4516 and Ex-miR-4674 were identified in PDAC patient PJ with high sensitivity and specificity.
- A triple assay (Ex-miR-4516/4674/PJ cytology) improved diagnostic accuracy to 88.5%.
- Serum Ex-miR-4516 showed 97.5% sensitivity for PDAC detection and decreased post-resection.
Conclusions:
- Ex-miR-4516, validated by in situ hybridization, shows significant potential for early PDAC detection.
- Liquid assays utilizing Ex-miR-4516 may aid in monitoring PDAC clinical course.
- The identified Ex-miRs represent promising biomarkers for PDAC diagnosis.
