Diagnostic and Metastatic Predictive Value of Urinary Exosomal miR-26b-3p in Prostate Cancer: A Prospective Observational Study

Authors

  • Muhammad Sufriyudi Urology Resident, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia
  • HR Danarto Division of Urology, Department of Surgery, Faculty of Medicine, Public Health and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia

DOI:

https://doi.org/10.55018/janh.v8i2.636

Keywords:

Prostatic Neoplasms, Biomarkers, MicroRNAs, Urine, Exosomes, Metastasis

Abstract

Background: Prostate cancer (PCa) remains challenging to diagnose due to the limited accuracy of PSA testing. Urinary exosomal miR-26b-3p is a promising non-invasive biomarker, but evidence across PCa metastatic stages is limited, particularly in LMICs. This study evaluated miR-26b-3p expression in BPH, non-metastatic PCa, and metastatic PCa (M1b and M1c), and assessed its diagnostic and metastatic discrimination potential.

Methods: This prospective, observational, single-center study was conducted at Dr Sardjito General Hospital, Yogyakarta, Indonesia, from January 2023 to December 2023, and reported in accordance with the STROBE guidelines. A total of 40 male participants (12 BPH and 28 PCa) were enrolled using consecutive sampling. Inclusion criteria were men aged ≥40 years with histopathologically confirmed BPH or PCa who provided written informed consent. Exclusion criteria were prior pelvic radiotherapy, urinary tract infection, hematuria, or incomplete urine specimens. The independent variable was the clinical diagnostic group; the dependent variable was relative urinary exosomal miR-26b-3p expression. Urinary exosomes were isolated, and miR-26b-3p was quantified by quantitative real-time PCR (qPCR). Group comparisons used one-way ANOVA with post-hoc analysis, and diagnostic performance was evaluated by Receiver Operating Characteristic (ROC) analysis with Area Under the Curve (AUC) and 95% confidence interval (CI).

Results: miR-26b-3p expression differed significantly among the four groups (p = 0.002). Mean ± SD expression was 6.6 ± 3.4 in BPH, 44.2 ± 25.4 in non-metastatic PCa, 46.7 ± 41.1 in M1b PCa, and 35.1 ± 21.3 in M1c PCa. ROC analysis demonstrated excellent diagnostic performance for differentiating BPH from PCa (AUC = 0.982; 95% CI: 0.943–1.000; p < 0.001).

Conclusion: Urinary exosomal miR-26b-3p shows strong diagnostic discrimination between BPH and PCa and is associated with metastatic status, supporting its potential as a non-invasive biomarker for prostate cancer screening and metastatic risk stratification. Multicenter validation in larger, ethnically diverse cohorts is needed before clinical implementation.

Downloads

Download data is not yet available.

References

Global Cancer Observatory. (2022). Indonesia cancer factsheet. International Agency for Research on Cancer. https://gco.iarc.fr/today/en

Van Blarigan, E. L., McKinley, M. A., Washington, S. L., Cooperberg, M. R., Kenfield, S. A., Cheng, I., et al. (2025). Trends in prostate cancer incidence and mortality rates. JAMA Network Open, 8(1), e2456825. https://doi.org/10.1001/jamanetworkopen.2024.56825

Wang, L., Lu, B., He, M., Wang, Y., Wang, Z., & Du, L. (2022). Prostate cancer incidence and mortality: Global status and temporal trends in 89 countries from 2000 to 2019. Frontiers in Public Health, 10, 811044. https://doi.org/10.3389/fpubh.2022.811044

Harati, R., Mabondzo, A., Tlili, A., Khoder, G., Mahfood, M., & Hamoudi, R. (2021). Combinatorial targeting of microRNA-26b and microRNA-101 exerts a synergistic inhibition on cyclooxygenase-2 in brain metastatic triple-negative breast cancer cells. Breast Cancer Research and Treatment, 187(3), 695–713. https://doi.org/10.1007/s10549-021-06255-y

Cochetti, G., Poli, G., Guelfi, G., Boni, A., Egidi, M. G., & Mearini, E. (2016). Different levels of serum microRNAs in prostate cancer and benign prostatic hyperplasia: Evaluation of potential diagnostic and prognostic role. OncoTargets and Therapy, 9, 7545–7553. https://doi.org/10.2147/OTT.S119027

Shaw, G., & Almeida-Magana, R. (2025). Prostate cancer diagnosis, classification and treatment overview. Surgery (Oxford), 43(2), 70–78. https://doi.org/10.1016/j.mpsur.2025.01.005

Bian, Z., Huang, X., Chen, Y., Meng, J., Feng, X., Zhang, M., et al. (2021). Fifteen-miRNA-based signature is a reliable prognosis-predicting tool for prostate cancer patients. International Journal of Medical Sciences, 18(1), 284–294. https://doi.org/10.7150/ijms.49412

Mello-Grand, M., Bruno, A., Sacchetto, L., Brescia, I., Gontero, P., Zitella, A., Scapoli, C., & Chiorino, G. (2021). Two novel ceRNA networks as potential prognostic biomarkers for prostate cancer. Cancers, 13(19), 4940. https://doi.org/10.3390/cancers13194940

Zhang, Y., Zhang, D., Li, Q., Liang, J., Sun, L., Yi, X., et al. (2022). Urinary exosomal microRNAs as biomarkers for the diagnosis and prognosis of prostate cancer. Frontiers in Oncology, 12, 968165. https://doi.org/10.3389/fonc.2022.968165

Liu, D., Kuai, Y., Zhu, R., Zhou, C., Tao, Y., Han, W., et al. (2020). Prognosis of prostate cancer and bone metastasis pattern of patients: A SEER-based study and a local hospital based study from China. Scientific Reports, 10(1), 9104. https://doi.org/10.1038/s41598-020-64073-6

Borley, N., & Feneley, M. R. (2009). Prostate cancer: Diagnosis and staging. Asian Journal of Andrology, 11(1), 74–80. https://doi.org/10.1038/aja.2008.19

Bardoscia, L., Sardaro, A., Quattrocchi, M., Cocuzza, P., Ciurlia, E., Furfaro, I., et al. (2025). The evolving landscape of novel and old biomarkers in localized high-risk prostate cancer: State of the art, clinical utility, and limitations toward precision oncology. Journal of Personalized Medicine, 15(8), 367. https://doi.org/10.3390/jpm15080367

Barsouk, A., Padala, S. A., Vakiti, A., Mohammed, A., Saginala, K., Thandra, K. C., et al. (2020). Epidemiology, staging and management of prostate cancer. Medical Sciences, 8(3), 28. https://doi.org/10.3390/medsci8030028

Gomez-Acebo, I., Alonso-Molero, J., Fernandez-Ortiz, M., Dierssen-Sotos, T., Llorca, J., & Castaño-Vinyals, G. (2025). MicroRNA-26b family in prostate cancer: Mechanistic insights and clinical implications. Cancers, 17(4), 612. https://doi.org/10.3390/cancers17040612

Gordetsky, J., & Epstein, J. (2016). Grading of prostatic adenocarcinoma: Current state and prognostic implications. Diagnostic Pathology, 11(1), 25. https://doi.org/10.1186/s13000-016-0478-2

Pisapia, P., Pepe, F., Russo, G., Capoluongo, R., Coppola, M., Giudice, F. D., et al. (2025). Liquid biopsy testing in urological cancers: Focus on urine. Urologic Oncology: Seminars and Original Investigations, 43(10), 553–564. https://doi.org/10.1016/j.urolonc.2025.05.020

Juracek, J., Madrzyk, M., Stanik, M., & Slaby, O. (2022). Urinary microRNAs and their significance in prostate cancer diagnosis: A 5-year update. Cancers, 14(13), 3157. https://doi.org/10.3390/cancers14133157

Markert, L., Holdmann, J., Klinger, C., Kaufmann, M., Schork, K., Turewicz, M., Eisenacher, M., Saruhan-Direskeneli, G., Bonifacio, E., & Stenzl, A. (2022). Identification of urinary microRNAs as non-invasive biomarkers for prostate cancer detection. Cancers, 14(20), 4951. https://doi.org/10.3390/cancers14204951

Kato, M., Goto, Y., Matsushita, R., Kurozumi, A., Fukumoto, I., Nishikawa, R., et al. (2015). MicroRNA-26a/b directly regulates La-related protein 1 and inhibits cancer cell invasion in prostate cancer. International Journal of Oncology, 47(2), 710–718. https://doi.org/10.3892/ijo.2015.3043

Markert, L., Holdmann, J., Klinger, C., Kaufmann, M., Stenzl, A., & Todenhöfer, T. (2021). Urinary cell-free microRNA signature panel for prostate cancer diagnosis. Translational Andrology and Urology, 10(11), 4135–4148. https://doi.org/10.21037/tau-21-577

John Clotaire, D. Z., Zhang, B., Wei, N., Gao, R., Zhao, F., & Wang, Y. (2016). miR-26b inhibits autophagy by targeting ULK2 in prostate cancer cells. Biochemical and Biophysical Research Communications, 472(1), 194–200. https://doi.org/10.1016/j.bbrc.2016.02.093

Lin, Y., Sun, T., & Sun, G. (2022). High miR-34a and miR-26b expressions inhibit prostate cancer cell OPCN-1 proliferation and enhance apoptosis. Tropical Journal of Pharmaceutical Research, 21(2), 229–236. https://doi.org/10.4314/tjpr.v21i2.4

Garg, R., Blando, J. M., Perez, C. J., Lal, P., Feldman, M. D., Smyth, E. M., et al. (2018). COX-2 mediates pro-tumorigenic effects of PKCε in prostate cancer. Oncogene, 37(34), 4735–4749. https://doi.org/10.1038/s41388-018-0318-9

Rana, S., Valbuena, G. N., Curry, E., Bevan, C. L., & Keun, H. C. (2022). MicroRNAs as biomarkers for prostate cancer prognosis: A systematic review and a systematic reanalysis of public data. British Journal of Cancer, 126(3), 502–513. https://doi.org/10.1038/s41416-021-01620-6

Yurikova, O. Yu., Aisina, D. E., Niyazova, R. E., Atambayeva, Sh. A., Labeit, S., & Ivashchenko, A. T. (2019). The interaction of miRNA-5p and miRNA-3p with the mRNAs of orthologous genes. Molecular Biology, 53(4), 612–623. https://doi.org/10.1134/S0026893319040174

Cannistraci, A., Federici, G., Addario, A., Di Pace, A. L., Grassi, L., Muto, G., Collura, D., Signore, M., De Salvo, L., Sentinelli, S., Simone, G., Costantini, M., Nanni, S., Farsetti, A., Coppola, V., De Maria, R., & Bonci, D. (2023). miR-26b/TBX3 axis enhances prostate cancer aggressiveness. Cell Death Discovery, 9, 78. https://doi.org/10.1038/s41420-023-01385-2

Downloads

Published

2026-07-01

How to Cite

Sufriyudi, M. ., & Danarto, H. . (2026). Diagnostic and Metastatic Predictive Value of Urinary Exosomal miR-26b-3p in Prostate Cancer: A Prospective Observational Study. Journal of Applied Nursing and Health, 8(2), 1332–1340. https://doi.org/10.55018/janh.v8i2.636