Prostate Cancer Specific RNAs Identified in Urine and Tissue

Researchers have discovered a set of potential-biomarker RNAs that may pave the way to a more reliable prostate cancer (PrCa) screening assay.

A team led by Ranjan J. Perera, PhD, associate professor and scientific director of Analytical Genomics and Bioinformatics at the Lake Nona (Orlando, FA, USA) campus of the Sanford-Burnham Medical Research Institute (Orlando, FA and La Jolla, CA, USA) has identified a set of RNA molecules that are detectable in tissue samples and urine of PrCa patients but not in normal healthy individuals. The study sets the stage for development of more sensitive and specific noninvasive tests for PrCa than those currently available, which could result in fewer unnecessary biopsies and less treatment-related morbidity.

Since most men with PrCa have indolent (nonaggressive) disease for which conservative therapy or surveillance is appropriate, the challenge is not only PrCa diagnosis, but also how to distinguish between patients who would benefit from surgical or other aggressive treatment from those who would not. "While elevated PSA can be an alert to a lethal cancer, it can also detect less aggressive cancers that may never do any harm," said Vipul Patel, MD, medical director of the Global Robotics Institute at Florida Hospital in Orlando (USA), "Moreover, only 25% of men with raised PSA levels that have a biopsy actually have PrCa. PrCa needs to be screened for; we just need to find a better marker."

The team identified a group of long noncoding RNAs (lncRNAs) that may serve as better prognostic PrCa markers. Until recently lncRNAs were dismissed as irrelevant, but are now thought to regulate normal cellular development and are increasingly reported as contributing to various diseases, including cancer. "We have identified a set of lncRNAs that appear to have an important role in PrCa diagnostics," said Prof. Perera, "The findings advance our understanding of the role of lncRNAs in cancer biology and, importantly, broaden the opportunity to use lncRNAs as biomarkers."

The study profiled the lncRNAs in 3 distinct groups: (1) human PrCa cell lines and normal prostate epithelial cells; (2) prostate adenocarcinoma tissue samples and matched normal tissue samples; and (3) urine samples from patients with PrCa or benign prostate hyperplasia, and normal healthy individuals. In each case, the lncRNAs were elevated in PrCa patient samples—but not in patients with benign prostate hyperplasia or normal healthy individuals.

One advantage of lncRNAs is that they can be detected in urine, more easily available than blood. One lncRNA, PCA3, was recently commercialized in a urine test to identify which men suspected of having PrCa should undergo repeat prostate biopsy. However, discrepancies exist between PCA3 levels and clinicopathologic features. In the current study, PCA3 was detected in some but not all samples, suggesting that reliance on a single biomarker may be insufficient for PrCa detection.

"There is a tremendous unmet clinical need for better noninvasive screening tools for early detection of PrCa to reduce the overtreatment and morbidity of this disease," added Dr. Patel, "Our findings represent a promising approach to meet this demand."

The study, by Lee B, Mazar J, et al., was published October 2014, online ahead of print, in the Journal of Molecular Diagnostics, of the Association for Molecular Pathology (AMP).

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Sanford-Burnham Medical Research Institute