Evaluation of Exosome-derived Small RNAs as Potential Biomarkers for Pancreatic Ductal Adenocarcinoma Using Next-generation Sequencing
- Author:
Hyemin KIM
1
;
Sabin PARK
;
Myung Ji GOH
;
Young Hoon CHOI
;
Minjee KIM
;
Jin Ho CHOI
;
Jung Hyun KIM
;
Eun Mi LEE
;
Se-Hoon LEE
;
Kyu Taek LEE
;
Kwang Hyuk LEE
;
Jong Kyun LEE
;
Semin LEE
;
Joo Kyung PARK
Author Information
- Publication Type:Original Article
- From:Annals of Laboratory Medicine 2025;45(6):609-619
- CountryRepublic of Korea
- Language:English
-
Abstract:
Background:Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and lacks clinical biomarkers. Exosomes are extracellular vesicles that facilitate cell–cell communication by distributing macromolecules, such as small RNAs (smRNAs). We assessed the potential of exosome-derived small RNAs (Ex-smRNAs) as PDAC biomarkers.
Methods:Peripheral blood was collected from 51 patients with PDAC and 15 control individuals. Exosomes were isolated using an aqueous two-phase system. Ex-smRNAs were analyzed using smRNA sequencing. smRNA-mediated target gene regulation was verified via The Cancer Genome Atlas analysis and in vitro transfection and wound-healing assays using PDAC organoids.
Results:The total Ex-smRNA count was substantially reduced in patients with PDAC compared with that in control individuals. The levels of microRNAs (miRNAs) miR-125a-5p, miR-30e-5p, miR-16-2-3p, miR-98-5p, and the let-7 family were significantly suppressed, whereas that of miR-6731-5p was significantly elevated. Let-7c-5p and miR-98-5p were found to interact with the long non-coding RNA OLMALINC to regulate their common target genes, BACH1 and CCND1, thus controlling PDAC proliferation and migration. The expressions of CARS1-AS1 and miR-142-5p were upregulated in treatment-responsive patients.Multivariable Cox regression analyses, adjusting for potential prognostic factors such as sex, Eastern Cooperative Oncology Group performance status, and tumor size and stage, revealed that CARS1-AS1 (adjusted hazard ratio [HR] 0.33; 95% confidence interval [CI], 0.15–0.73; P = 0.0061) and miR-142-5p (adjusted HR 0.79; 95% CI, 0.61–1.01; P = 0.0581) were associated with improved overall survival.
Conclusions:We identified potential Ex-smRNA biomarkers involved in PDAC progression and prognosis that reflect key molecular alterations in PDAC and may serve as clinically relevant biomarkers for disease monitoring.
