Long Non-Coding RNA Predicts Prostate Cancer Metastases

Genetic marker indicates the 10-year risk of metastatic disease after treatment for localised prostate cancer

medwireNews: Expression of the long non-coding RNA SChLAP1 is significantly associated with the long-term risk of distant disease in men after prostate cancer surgery, research suggests.

Men with high expression of this Gene were almost 2.5 times more likely to develop metastases within 10 years of undergoing radical prostatectomy for localised prostate cancer than those with low expression, say Felix Feng, from the University of Michigan in Ann Arbor, USA, and team.

Analysis of a sample database with 35 different types of cancer and tissues specimens indicated that SChLAP1 was expressed only by prostate cancer cells, but levels of SChLAP1 in urine sediment samples significantly correlated with tissue levels.

“The fact that SChLAP1 is tissue specific is unique among potential prognostic biomarkers for prostate cancer and could lead to the development of non-invasive urine tests”, they write in The Lancet Oncology.

Using prostate cancer samples taken from 545 US patients, the team identified SChLAP1 as the most commonly overexpressed gene in samples from the 212 patients who went on to develop metastatic disease compared with the 333 patients who did not.

This finding was then confirmed in three separate validation cohorts of US and European prostate cancer patients, with high SChLAP1 expression significantly linked to a shorter time to metastases and biochemical relapse, as well as an increased risk of prostate cancer-specific mortality.

SChLAP1 expression was also significantly associated with risk factors for aggressive disease, the researchers found, including a positive surgical margin, extracapsular disease and seminal vesicle invasion.

Multivariate analysis showed that high SChLAP1 expression was significantly associated with the 10-year risk of metastases after radical prostatectomy (odds ratio [OR]=2.45), the 5-year risk of biochemical recurrence (OR=1.76) and 10-year all-cause mortality (OR=1.93) compared with low expression.

Thus, SChLAP1 expression had comparable prognostic power to a Gleason score of 8 to 10 versus 5 to 7 for the risk of these three outcomes (OR=2.14, 1.56 and 2.06, respectively).

“We hope that measurement of SChLAP1 expression becomes a component of future prospective clinical trials, and we believe that patients with prostate cancer with high SChLAP1 expression should be enrolled in clinical trials of intensive adjuvant treatment”, write Felix Feng et al.

Reference

Prensner JR, Zhao S, Erho N, et al. RNA biomarkers associated with metastatic progression in prostate cancer: a multi-institutional high-throughput analysis of SChLAP1. Lancet Oncol 2014; Early online publication 17 November. doi:10.1016/S1470-2045(14)71113-1

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