MicroRNA (miRNA) found in seminal fluid (SF) may be a diagnostically useful maker of prostate cancer, according to a proof-of-principle study published online ahead of print May 23 in Endocrine-Related Cancer. If, with further validation, these biomarkers continue to show that they that can accurately identify prostate cancer at an early stage and identify aggressive disease subtypes, it would be an important step in improving patient management, the authors say. Using small RNA sequencing (Illumina’s TruSeq Small RNA work-flow) and quantitative real-time polymerase chain reaction, the Australian researchers analyzed the RNA population in the nonsperm cellular portion of SF. In the discovery phase, comparisons were made between RNA men with low- or intermediate-risk cancer and men without cancer. All had elevated prostate-specific antigen (PSA) levels. Identified miRNA biomarkers were then validated in a subsequent cohort of 26 men with biopsy-proven, low-high risk tumors and 22 men with elevated PSA, but no detectable cancer on biopsy. The researchers found that the RNA of the nonsperm SF cellular fraction consisted primarily of transfer RNA (tRNA) and miRNA, with a higher ratio of tRNA to miRNA among men with cancer compared to controls. A filtering strategy applied to robustly expressed miRNA identified 82 […]
MicroRNA (miRNA) found in seminal fluid (SF) may be a diagnostically useful maker of prostate cancer, according to a proof-of-principle study published online ahead of print May 23 in Endocrine-Related Cancer. If, with further validation, these biomarkers continue to show that they that can accurately identify prostate cancer at an early stage and identify aggressive disease subtypes, it would be an important step in improving patient management, the authors say.
Using small RNA sequencing (Illumina’s TruSeq Small RNA work-flow) and quantitative real-time polymerase chain reaction, the Australian researchers analyzed the RNA population in the nonsperm cellular portion of SF. In the discovery phase, comparisons were made between RNA men with low- or intermediate-risk cancer and men without cancer. All had elevated prostate-specific antigen (PSA) levels. Identified miRNA biomarkers were then validated in a subsequent cohort of 26 men with biopsy-proven, low-high risk tumors and 22 men with elevated PSA, but no detectable cancer on biopsy.
The researchers found that the RNA of the nonsperm SF cellular fraction consisted primarily of transfer RNA (tRNA) and miRNA, with a higher ratio of tRNA to miRNA among men with cancer compared to controls. A filtering strategy applied to robustly expressed miRNA identified 82 miRNAs that were differentially expressed in prostate cancer (20 increased and 62 decreased). Applying the potential miRNA biomarkers (those elevated in PCa) to the validation cohort showed five miRNA markers were present at significantly higher levels in cancer samples.
All of the miRNAs were able to more accurately discriminate between cancer and noncancer than serum PSA, although miR-200b was the only significantly discriminatory marker. An additive diagnostic benefit of multiple miRNAs was lacking. Furthermore, none of the miRNAs correlated with serum PSA levels. The combination of miR-200b and serum PSA was significantly better at identifying men with cancer than PSA alone.
“SF miRNA measurements could be used to help determine if or when to proceed with curative interventions by providing an additional measure of global prostatic pathology, with a clear advantage of repeated and non-invasive sampling,” write the authors, led by Luke A. Selth, from University of Adelaide in Australia. “SF miRNAs could be used in combination with other emerging molecular tools, such as urine TMPRSS2:ERG and PCA3, to provide a more robust appraisal of the likelihood of clinically significant disease. Second, SF miRNAs could have a role as a non-invasive tool for monitoring men in active surveillance regimens, a management approach now adopted worldwide for low risk prostate cancer.”
Takeaway: While larger validation studies are warranted, prostate cancer experts are encouraged by the complimentary diagnostic benefit afforded by miRNA from seminal fluid.
