New Biomarkers to Distinguish Benign Prostatic Hyperplasia, Precancerous Lesions, and Prostate Cancer

A recent study has explored the diagnostic value of certain circulating and exosome-derived molecular markers to better differentiate between three prostate conditions: benign prostatic hyperplasia (BPH), precancerous lesions (PL), and prostate cancer (PCa).

The researchers focused on a group of molecules already known for their role in key cellular processes such as stress response, programmed cell death (apoptosis), inflammation, and tumor progression. These include two mitochondrial-derived peptides (Humanin and MOTS-c), a long non-coding RNA (GAS5), and two exosome-carried microRNAs (miR-21 and miR-103).

The study enrolled 375 men with suspected prostate cancer. Plasma samples were analyzed for Humanin, MOTS-c, and GAS5, while exosomal microRNAs were extracted and measured. The diagnostic accuracy of these markers—both individually and in combination—was assessed using advanced statistical tools, including ROC curve analysis and decision tree models.

Key findings include:

• Humanin and GAS5 were significantly reduced in both precancerous lesions and prostate cancer compared to BPH, suggesting they may play a role in the early transition toward disease.
• miR-21 and miR-103 were markedly increased in prostate cancer, with miR-21 showing exceptional accuracy in distinguishing between the different stages of prostate disease (with near-perfect performance).
• MOTS-clevels were higher in precancerous lesions than in BPH, pointing to a possible role in the early steps of malignant transformation.

When Humanin, GAS5, and MOTS-c were combined into a plasma-only model, the researchers achieved a 95% classification accuracy in differentiating the clinical groups.

These results highlight the potential of an integrated panel of circulating and exosomal biomarkers as a promising non-invasive tool for risk stratification in prostate diseases. If further validated, this strategy could improve diagnostic precision and support more personalized clinical decision-making in prostate cancer management.