Liquid Biopsy-Based Exo-oncomiRNAs Can Predict Prostate Cancer Aggressiveness

Abstract

Liquid biopsy-based biomarkers, including microRNAs packaged within extracellular vesicles, are promising tools for patient management. The cytokine tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is related to PCa progression and is found in the semen of patients with PCa. TWEAK can induce the transfer of exo-oncomiRNAs from tumor cells to body fluids, and this process might have utility in non-invasive PCa prognosis. We investigated TWEAK-regulated exo-microRNAs in semen and in post-digital rectal examination urine from patients with different degrees of PCa aggressiveness. We first identified 14 exo-oncomiRNAs regulated by TWEAK in PCa cells in vitro, and subsequently validated those using liquid biopsies from 97 patients with PCa. Exo-oncomiR-221-3p, -222-3p and -31-5p were significantly higher in the semen of high-risk patients than in low-risk peers, whereas exo-oncomiR-193-3p and -423-5p were significantly lower in paired samples of post-digital rectal examination urine. A panel of semen biomarkers comprising exo-oncomiR-221-3p, -222-3p and TWEAK was designed that could correctly classify 87.5% of patients with aggressive PCa, with 85.7% specificity and 76.9% sensitivity with an area under the curve of 0.857. We additionally found that TWEAK modulated two exo-oncomiR-221-3p targets, TCF12 and NLK. Overall, we show that liquid biopsy detection of TWEAK-regulated exo-oncomiRNAs can improve PCa prognosis prediction.

A New Approach for Prostate Cancer Diagnosis by miRNA Profiling of Prostate-Derived Plasma Small Extracellular Vesicles

“…miRNA was isolated from the general population and from the PSMA(+)SEVs in parallel. We selected four miRNAs involved in PC development: mir-141 [ 22 ], mir-145 [ 22 ], mir-221 [ 23 ], and mir-451a [ 24 ]. Mir-141 is reported to be consistently up-regulated in PC compared with healthy controls and has been suggested as a biomarker for biochemical failure and clinical outcome [ 25 ].…”

Tumor Suppressive Circular RNA-102450: Development of a Novel Diagnostic Procedure for Lymph Node Metastasis from Oral Cancer

“…LB of body fluids is commonly used for the diagnosis of multiple human diseases [36,37]. Although miRNAs have been widely assessed as biomarkers in body fluids [38,39], it was recently reported that circRNAs are highly resistant to RNA degradation by exonucleases compared with miRNAs [4,9,10]. CircRNAs are also widely distributed not only within cells but in the extracellular space and various body fluids [26,40].…”

Anti-Cancer Role and Therapeutic Potential of Extracellular Vesicles

“…MiR-21, miR-375, and miR-204 have been detected in the urine of prostate cancer patients but not in healthy donors [ 81 ]. It has been reported that the levels of miR-221-3p, miR-222-3p, and miR31-5p are higher in high-risk patients compared to low-risk patients [ 85 ]. EV proteins are also useful as biomarkers of prostate cancer.…”