Can specific miRNAs be used to predict risk of early biochemical relapse after first-line treatment?

No currently known biomarker can accurately predict the risk of prostate cancer recurrence at the time of or immediately following first-line treatment for localized prostate cancer. The best we can currently manage is to track a patient’s PSA level and his PSA doubling time. This is a real clinical problem, particularly for those men who fall into the intermediate- and high-risk prostate cancer categories at the time of diagnosis.

We also have no way of knowing when a rising PSA is really clinically significant in many individual patients, and we use rather arbitrary cut-off levels (e.g., 0.2 ng/ml after a radical prostatectomy) to decide when a man may need second-line therapy. But a man who takes 5 years to achieve a PSA level of 0.2 ng/ml in a series of very small steps may be in a very different risk category than a man who suddenly goes from a PSA of < 0.003 to 0.3 ng/ml within 3 months at (say) 3 years after surgery.

Fendler et al. have made an initial attempt to assess the potential of mitochondrial RNA molecules (miRNAs) as reliable predictive markers for biochemical recurrence of prostate cancer at < 1 year (early) or ≥ 2 years (late) following a radical prostatectomy. To do this, they used tissue samples from 52 primary prostate cancers and normal adjacent tissues obtained after the surgery. They then used real-time quantitative polymerase chain reaction (RT-qPCR) analysis to identify a miRNA signature that could predict relapse and to validate their findings.

Here is a quick summary of their findings:

  • They identified 63 miRNAs that were differentially expressed among the same categories of patients.
    • 35/63 miRNAs (55 percent) were up-regulated (found in greater amounts after surgery)
    • 28/63 miRNAs (45 percent) were down-regulated (found in lesser amounts after surgery).
  • Many of these miRNAs have pre-established prognostic significance in other cancers and may be actively involved in cancer progression.
  • Predicted targets of these miRNAs could be involved in biological processes and pathways that enhance cancer progression.
  • The role of one of the dysregulated miRNAs (miR-10b) in biochemical recurrence was validated using a cancer proliferation and wound-healing assay. 

The authors conclude that miRNAs could potentially have a role as reliable predictive markers for biochemical relapse of prostate cancer (at least at the time of radical prostatectomy).

Obviously this is a very preliminary study, but if it was truly possible to identify miRNA signatures of patients that could be used to predict risk of real biochemical recurrence of clinically significant prostate cancer at (say) < 2 years, 2 to 5 years, and 5 to 10 years post-treatment, these would be a set of very valuable prognostic tools.

3 Responses

  1. Assuming it becomes a good prognostic tool, it seems that unless a treatment is developed for those who will, for example, relapse sooner rather than later, what use will there be for the new tool? Please explain why the tool will be “valuable.” Because an early relapse prediction should discourage treatment with a radical prostatectomy and encourage treatment with radiation therapy? Or would the prognostic tool show that in fact the cancer is not localized at the time of diagnosis?

    Richard S.

  2. Richard:

    If I could tell you and your doctor, 2 weeks after surgery (or perhaps even before any form of treatment) that you had a 75% probability of biochemical recurrence within 2 years after first-line treatment, wouldn’t that help you to make decisions about how aggressive you wanted to be regarding having (say) immediate adjuvant radiation on top of surgery? Of course we need better treatments for progressive disease … but we also need to know which patients to use them in as early as possible. Currently most men who have first-line radiation therapy may not find out that they have recurrent disease until some 4 years after their first-line therapy because PSA is such a pooor marker for recurrence after radiation therapy.

  3. Thank you for the explanation. Your insight has helped me to think about the possibilities of what the existence of miRNA’s evidence: locally advanced extracapsular extension and/or distant micro-metastasis probabilities.

    Richard S.

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