Observational Study
Copyright ©The Author(s) 2025. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 14, 2025; 31(26): 109500
Published online Jul 14, 2025. doi: 10.3748/wjg.v31.i26.109500
Serum exosomal hsa-let-7f-5p: A potential diagnostic biomarker for metastatic pancreatic cancer detection
Shuai Ren, Li-Na Song, Rui Zhao, Ying Tian, Zhong-Qiu Wang
Shuai Ren, Li-Na Song, Rui Zhao, Ying Tian, Zhong-Qiu Wang, Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing 210029, Jiangsu Province, China
Co-corresponding authors: Ying Tian and Zhong-Qiu Wang.
Author contributions: Ren S, Tian Y, and Wang ZQ designed the research study; Ren S, Song LN, and Tian Y performed the research; Ren S and Song LN analyzed the data; Ren S and Zhao R wrote the manuscript; Tian Y and Wang ZQ revised the manuscript and made equal contributions as co-corresponding authors. All authors read and approved the final manuscript.
Supported by National Natural Science foundation of China, No. 82202135, No. 82371919, No. 82372017, and No. 82171925; Jiangsu Provincial Key research and development program, No. BE2023789; China Postdoctoral Science Foundation, No. 2023M741808; Young Elite Scientists Sponsorship Program by China Association of Chinese Medicine, No. 2024-QNRC2-B16; Young Elite Scientists Sponsorship Program by Jiangsu Association for Science and Technology, No. JSTJ-2023-WJ027; Science and Technology Planning Project of Jiangsu Province, No. BK20241994; Nanjing Postdoctoral Science Foundation, Natural Science Foundation of Nanjing University of Chinese Medicine, No. XZR2023036; Foundation of Excellent Young Doctor of Jiangsu Province Hospital of Chinese Medicine, No. 2023QB0112; and Jiangsu Provincial Science and Technology Resources (Clinical Resources) Coordination Service Platform, No. TC2023B003.
Institutional review board statement: This study was approved by the Ethics Committee of Affiliated Hospital of Nanjing University of Chinese Medicine, No. 2017NL-137-05.
Informed consent statement: Written informed consent was obtained from the participants.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
STROBE statement: The authors have read the STROBE Statement-checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-checklist of items.
Data sharing statement: Data is available upon reasonable request from the corresponding author.
Open Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhong-Qiu Wang, MD, PhD, Chief Physician, Director, Head, Professor, Department of Radiology, Jiangsu Province Hospital of Chinese Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, No. 155 Hanzhong Road, Nanjing 210029, Jiangsu Province, China. zhongqiuwang0815@163.com
Received: May 14, 2025
Revised: June 5, 2025
Accepted: June 30, 2025
Published online: July 14, 2025
Processing time: 59 Days and 5.2 Hours
Abstract
BACKGROUND

Exosomal microRNAs (miRNAs) have emerged as promising biomarkers for cancer diagnosis due to their stability, tumor specificity, and accessibility. However, the diagnostic potential of serum exosomal miRNAs in metastatic pancreatic cancer remains underexplored.

AIM

To investigate the diagnostic potential of serum exosomal miRNAs in metastatic pancreatic cancer.

METHODS

A total of 36 patients were enrolled, comprising 8 patients in the discovery phase (4 with metastatic and 4 with non-metastatic pancreatic cancer) and 28 in the validation cohort (15 non-metastatic and 13 metastatic cases). Exosomes were isolated using the exoEasy Maxi Kit and characterized by transmission electron microscopy, nanoparticle tracking analysis, and western blotting. High-throughput sequencing was conducted to identify differentially expressed serum exosomal miRNAs, which were subsequently validated using TaqMan probe-based reverse transcription-quantitative polymerase chain reaction. Bioinformatic analyses were performed to predict downstream target genes and explore their roles in metastatic progression.

RESULTS

Transmission electron microscopy revealed that the isolated exosomes were predominantly round or oval with well-defined membrane boundaries. Nanoparticle tracking analysis showed a peak particle size of approximately 138 nm, accounting for 99.2% of total particles, consistent with the typical size range of exosomes. Western blotting confirmed the expression of exosome-specific markers CD63 and CD81. High-throughput sequencing identified 42 differentially expressed exosomal miRNAs between metastatic and non-metastatic groups. Among them, hsa-let-7f-5p was significantly upregulated in metastatic pancreatic cancer (P = 0.007), as validated by reverse transcription-quantitative polymerase chain reaction. Target gene prediction indicated that hsa-let-7f-5p may be involved in metastasis through its interactions with nerve growth factor, cyclin-dependent kinase inhibitor 1A, high mobility group AT-hook 2, insulin-like growth factor 2 mRNA-binding protein 1, and insulin-like growth factor 2 mRNA-binding protein 3.

CONCLUSION

The elevated expression of serum exosomal hsa-let-7f-5p in metastatic pancreatic cancer suggests its potential as a non-invasive biomarker for distinguishing metastatic from non-metastatic disease.

Keywords: Serum exosomes; MicroRNA; Pancreatic cancer; Metastasis; Biomarker

Core Tip: Pancreatic cancer has a poor prognosis largely due to late-stage diagnosis and high metastatic potential. Exosomes, particularly exosome-derived microRNAs, have emerged as promising non-invasive biomarkers. This study identifies hsa-let-7f-5p as significantly upregulated in serum exosomes of metastatic pancreatic cancer patients. Validated through high-throughput sequencing and quantitative polymerase chain reaction, hsa-let-7f-5p shows potential for distinguishing metastatic from non-metastatic disease. Its target gene interactions further support its role in metastasis, offering new insights into pancreatic cancer progression and potential avenues for early detection and therapeutic intervention.