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

Area of Science:

• Oncology
• Biomarker Discovery
• Molecular Diagnostics

Background:

• Liquid biopsy biomarkers, particularly extracellular vesicle microRNAs, offer potential for non-invasive patient management.
• Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is implicated in prostate cancer (PCa) progression and can mediate the transfer of oncomiRNAs.

Purpose of the Study:

• To investigate TWEAK-regulated extracellular vesicle microRNAs in body fluids for improved PCa prognosis.
• To identify and validate specific exo-oncomiRNAs associated with PCa aggressiveness.

Main Methods:

• In vitro identification of TWEAK-regulated exo-oncomiRNAs in PCa cells.
• Validation of candidate biomarkers in semen and urine from 97 PCa patients.
• Development and evaluation of a diagnostic biomarker panel using receiver operating characteristic analysis.

Main Results:

• Three exo-oncomiRs (221-3p, 222-3p, 31-5p) were elevated in semen of high-risk PCa patients.
• Two exo-oncomiRs (193-3p, 423-5p) were decreased in urine of PCa patients.
• A semen biomarker panel (exo-oncomiR-221-3p, -222-3p, TWEAK) achieved an AUC of 0.857 for aggressive PCa classification.

Conclusions:

• TWEAK-mediated exo-oncomiRNAs in liquid biopsies can enhance PCa prognosis.
• Semen-based biomarkers, including TWEAK and specific exo-oncomiRs, show significant potential for non-invasive diagnosis of aggressive PCa.